RESUMEN
STUDY OBJECTIVE: To evaluate aerosol dispersion and exposure risk during oxygenation therapy among health care personnel. METHODS: This study compared the aerosol dispersion effect produced through continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), BiPAP with face coverings, a high-flow nasal cannula (HFNC) with face coverings, nasal cannula oxygenation (NCO) at 15 L/min with face coverings, nonrebreather mask (NRM), and ventilator-assisted preoxygenation (VAPOX) during oxygenation therapy at a minute ventilation of 10 L/min and 20 L/min. The length and width of aerosol dispersion were recorded, and aerosol concentrations were then detected at a mannequin's head, trunk, and feet. RESULTS: The average length dispersion distance of CPAP was 47.12 cm (SD, 12.56 cm), of BiPAP was 100.13 cm (SD, 6.03 cm), of BiPAP with face coverings was 62.20 cm (SD, 8.46 cm), of HFNC with face coverings was 67.09 cm (SD, 12.74 cm); of NCO with face coverings was 85.55 cm (SD, 7.28 cm); and of NRM was 63.08 cm (SD, 15.33 cm); VAPOX showed no visible dispersion. The aerosol concentrations at the feet under CPAP and at the head under BiPAP were significantly higher than those observed without an oxygen device. Compared with no oxygen device, the aerosol concentration with HFNC was higher at the mannequin's head, trunk, and feet; whereas it was lower with VAPOX and NRM. Moreover, when translated to the number of virus particles required to infect medical personnel (Nf), VAPOX took more time to achieve Nf than other devices. CONCLUSION: Strong flow from the oxygenation devices resulted in increased aerosol concentrations. CPAP at the feet side, BiPAP at the head side, HFNC, and NCO with face coverings significantly increase aerosol exposure and should be used with caution. Aerosol concentrations at all positions were lower with NRM and VAPOX.
Asunto(s)
Cánula , Ventilación no Invasiva , Aerosoles , Presión de las Vías Aéreas Positiva Contínua , Humanos , Oxígeno , Terapia por Inhalación de Oxígeno/métodos , Ventiladores MecánicosRESUMEN
Oxyhemoglobin saturation by pulse oximetry (SpO2) has always played an important role in the diagnosis of symptoms. Considering that the traditional SpO2 measurement has a certain error due to the number of wavelengths and the algorithm and the wider application of machine learning and spectrum combination, we propose to use 12-wavelength spectral absorption measurement to improve the accuracy of SpO2 measurement. To investigate the multiple spectral regions for deep learning for SpO2 measurement, three datasets for training and verification were built, which were constructed over the spectra of first region, second region, and full region and their sub-regions, respectively. For each region under the procedures of optimization of our model, a thorough of investigation of hyperparameters is proceeded. Additionally, data augmentation is preformed to expand dataset with added noise randomly, increasing the diversity of data and improving the generalization of the neural network. After that, the established dataset is input to a one dimensional convolution neural network (1D-CNN) to obtain a measurement model of SpO2. In order to enhance the model accuracy, GridSearchCV and Bayesian optimization are applied to optimize the hyperparameters. The optimal accuracies of proposed model optimized by GridSearchCV and Bayesian Optimization is 89.3% and 99.4%, respectively, and trained with the dataset at the spectral region of six wavelengths including 650 nm, 680 nm, 730 nm, 760 nm, 810 nm, 860 nm. The total relative error of the best model is only 0.46%, optimized by Bayesian optimization. Although the spectral measurement with more features can improve the resolution ability of the neural network, the results reveal that the training with the dataset of the shorter six wavelength is redundant. This analysis shows that it is very important to construct an effective 1D-CNN model area for spectral measurement using the appropriate spectral ranges and number of wavelengths. It shows that our proposed 1D-CNN model gives a new and feasible approach to measure SpO2 based on multi-wavelength.
Asunto(s)
Aprendizaje Profundo , Teorema de Bayes , Aprendizaje Automático , Redes Neurales de la Computación , OximetríaRESUMEN
Rice blast is a serious threat to global rice production. Large-scale and long-term cultivation of rice varieties with a single blast resistance gene usually leads to breakdown of resistance. To effectively control rice blast in Taiwan, marker-assisted backcrossing was conducted to develop monogenic lines carrying different blast resistance genes in the genetic background of an elite japonica rice cultivar, Kaohsiung 145 (KH145). Eleven International Rice Research Institute (IRRI)-bred blast-resistant lines (IRBLs) showing broad-spectrum resistance to local Pyricularia oryzae isolates were used as resistance donors. Sequencing analysis revealed that the recurrent parent, KH145, does not carry known resistance alleles at the target Pi2/9, Pik, Pita, and Ptr loci. For each IRBL × KH145 cross, we screened 21 to 370 (average of 108) plants per generation from the BC1F1 to BC3F1/BC4F1 generation. A total of 1,499 BC3F2/BC4F2 lines carrying homozygous resistance alleles were selected and self-crossed for four to six successive generations. The derived lines were also evaluated for background genotype using genotyping by sequencing, for blast resistance under artificial inoculation and natural infection conditions, and for agronomic performance in multiple field trials. In Chiayi and Taitung blast nurseries in 2018 to 2020, Pi2, Pi9, and Ptr conferred high resistance, Pi20 and Pik-h moderate resistance, and Pi1, Pi7, Pik-p, and Pik susceptibility to leaf blast; only Pi2, Pi9, and Ptr conferred effective resistance against panicle blast. The monogenic lines showed agronomic traits, yield, and grain quality similar to those of KH145, suggesting the potential of growing a mixture of lines to achieve durable resistance in the field.
Asunto(s)
Resistencia a la Enfermedad/genética , Magnaporthe , Oryza , Enfermedades de las Plantas , Genotipo , Oryza/genética , Oryza/microbiología , Fitomejoramiento , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiologíaRESUMEN
Breast tumors reprogram their cellular metabolism, nutrient uptake, and utilization-associated biochemical processes. These processes become further transformed as genetically predisposed metastatic breast tumor cells colonize specific organs. Breast tumor cells often metastasize to the brain, bone, lung and liver. Massagué and colleagues isolated organotropic subclones and established organ-specific gene signatures associated with lung-, bone-, and brain-specific metastatic triple-negative breast cancer (TNBC) MDA-MB-231 cells. Using these genetically characterized metastatic subclones specific to lung (LM4175), bone (BoM1833), and brain (BrM-2a), we evaluated marine natural products for the ability to differentially suppress metastatic breast cancer cells in a target organ-dependent manner. Psammaplin-based histone deacetylase (HDAC) inhibitors were found to differentially inhibit HDAC activity, induce activation of hypoxia-inducible factor-1 (HIF-1), and disrupt organotropic metastatic TNBC subclone growth. Further, psammaplins distinctly suppressed the outgrowth of BoM1833 tumor spheroids in 3D-culture systems. Similar results were observed with the prototypical HDAC inhibitor trichostatin A (TSA). These organotropic tumor cell-based studies suggest the potential application of HDAC inhibitors that may yield new directions for anti-metastatic breast tumor research and drug discovery.
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Antineoplásicos/farmacología , Organismos Acuáticos , Disulfuros/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Poríferos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Tirosina/análogos & derivados , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Técnicas de Cultivo/métodos , Disulfuros/química , Disulfuros/aislamiento & purificación , Disulfuros/uso terapéutico , Descubrimiento de Drogas/métodos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Femenino , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/aislamiento & purificación , Inhibidores de Histona Desacetilasas/uso terapéutico , Histona Desacetilasas/metabolismo , Humanos , Esferoides Celulares , Tirosina/química , Tirosina/aislamiento & purificación , Tirosina/farmacología , Tirosina/uso terapéuticoRESUMEN
Merocyclophanes C and D (1 and 2) were isolated from the cell extract of the cultured cyanobacterium UIC 10110. The structures were determined by one-dimensional nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry and confirmed by 2D NMR techniques. The absolute configurations were determined using electronic circular dichroism spectroscopy. Merocyclophanes C and D represent the first known analogues of the merocyclophane core structure, a recently discovered scaffold of [7,7] paracyclophanes characterized by an α-branched methyl at C-1/C-14; 1 and 2 showed antiproliferative activity against the MDA-MB-435 cell line with IC50 values of 1.6 and 0.9 µM, respectively. Partial 16S analysis determined UIC 10110 to be a Nostoc sp., and it was found to clade with UIC 10062 Nostoc sp., the only other strain known to produce merocyclophanes. The genome of UIC 10110 was sequenced, and a biosynthetic gene cluster was identified that is proposed to encode type I and type III polyketide synthases that are potentially responsible for production of the merocyclophanes; however, further experiments will be required to verify the true function of the gene cluster. The gene cluster provides a genetic basis for the observed structural differences of the [7,7] paracyclophane core structures.
Asunto(s)
Compuestos Macrocíclicos/aislamiento & purificación , Nostoc/química , Animales , Antibacterianos/química , Colorado , Agua Dulce/microbiología , Concentración 50 Inhibidora , Compuestos Macrocíclicos/química , Ratones , Estructura Molecular , Nostoc/genética , Resonancia Magnética Nuclear Biomolecular , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
(+)-Strebloside, a cardiac glycoside isolated from the stem bark of Streblus asper collected in Vietnam, has shown some potential for further investigation as an antineoplastic agent. A mechanistic study using an in vitro assay and molecular docking analysis indicated that (+)-strebloside binds and inhibits Na+/K+-ATPase in a similar manner to digitoxin. Inhibition of growth of different high-grade serous ovarian cancer cells including OVCAR3, OVSAHO, Kuramochi, OVCAR4, OVCAR5, and OVCAR8 resulted from treatment with (+)-strebloside. Furthermore, this compound blocked cell cycle progression at the G2 phase and induced PARP cleavage, indicating apoptosis activation in OVCAR3 cells. (+)-Strebloside potently inhibited mutant p53 expression through the induction of ERK pathways and inhibited NF-κB activity in human ovarian cancer cells. However, in spite of its antitumor potential, the overall biological activity of (+)-strebloside must be regarded as being typical of better-known cardiac glycosides such as digoxin and ouabain. Further chemical alteration of cardiac glycosides might help to reduce negative side effects while increasing cancer cell cytotoxicity.
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Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Glicósidos Cardíacos/aislamiento & purificación , Glicósidos Cardíacos/farmacología , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Carcinoma Epitelial de Ovario , Glicósidos Cardíacos/química , Digoxina/farmacología , Femenino , Células HT29 , Humanos , Estructura Molecular , FN-kappa B/metabolismo , Neoplasias Glandulares y Epiteliales , Ouabaína/farmacología , Neoplasias Ováricas , Transducción de Señal/efectos de los fármacos , EstereoisomerismoRESUMEN
Three new (1-3) and two known (4 and 5) cytotoxic cardiac glycosides were isolated and characterized from a medicinal plant, Streblus asper Lour. (Moraceae), collected in Vietnam, with six new analogues and one known derivative (5a-g) synthesized from (+)-strebloside (5). A preliminary structure-activity relationship study indicated that the C-10 formyl and C-5 and C-14 hydroxy groups and C-3 sugar unit play important roles in the mediation of the cytotoxicity of (+)-strebloside (5) against HT-29 human colon cancer cells. When evaluated in NCr nu/nu mice implanted intraperitoneally with hollow fibers facilitated with either MDA-MB-231 human breast or OVCAR3 human ovarian cancer cells, (+)-strebloside (5) showed significant cell growth inhibitory activity in both cases, in the dose range 5-30 mg/kg.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Glicósidos Cardíacos/aislamiento & purificación , Glicósidos Cardíacos/farmacología , Moraceae/química , Animales , Antineoplásicos Fitogénicos/química , Glicósidos Cardíacos/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Humanos , Ratones , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Plantas Medicinales , Relación Estructura-Actividad , VietnamRESUMEN
BACKGROUND: Silvestrol is a cyclopenta[b]benzofuran that was isolated from the fruits and twigs of Aglaia foveolata, a plant indigenous to Borneo in Southeast Asia. The purpose of the current study was to determine if inhibition of protein synthesis caused by silvestrol triggers autophagy and apoptosis in cultured human cancer cells derived from solid tumors. METHODS: In vitro cell viability, flow cytometry, fluorescence microscopy, qPCR and immunoblot was used to study the mechanism of action of silvestrol in MDA-MB-435 melanoma cells. RESULTS: By 24 h, a decrease in cyclin B and cyclin D expression was observed in silvestrol-treated cells relative to control. In addition, silvestrol blocked progression through the cell cycle at the G2-phase. In silvestrol-treated cells, DAPI staining of nuclear chromatin displayed nucleosomal fragments. Annexin V staining demonstrated an increase in apoptotic cells after silvestrol treatment. Silvestrol induced caspase-3 activation and apoptotic cell death in a time- and dose-dependent manner. Furthermore, both silvestrol and SAHA enhanced autophagosome formation in MDA-MB-435 cells. MDA-MB-435 cells responded to silvestrol treatment with accumulation of LC3-II and time-dependent p62 degradation. Bafilomycin A, an autophagy inhibitor, resulted in the accumulation of LC3 in cells treated with silvestrol. Silvestrol-mediated cell death was attenuated in ATG7-null mouse embryonic fibroblasts (MEFs) lacking a functional autophagy protein. CONCLUSIONS: Silvestrol potently inhibits cell growth and induces cell death in human melanoma cells through induction of early autophagy and caspase-mediated apoptosis. Silvestrol represents a natural product scaffold that exhibits potent cytotoxic activity and could be used for the further study of autophagy and its relationship to apoptosis in cancer cells.
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Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Caspasa 3/biosíntesis , Melanoma/tratamiento farmacológico , Triterpenos/administración & dosificación , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Caspasa 3/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina B/biosíntesis , Ciclina D/biosíntesis , Regulación Neoplásica de la Expresión Génica , Humanos , Macrólidos/administración & dosificación , Melanoma/genética , Melanoma/patología , RatonesRESUMEN
Six new pimarane derivatives, including two di-nor-pimaranes (1, 2), two 17-nor-pimaranes (3, 4), and two 17-nor-(9ß-H)-pimaranes (5, 6), were isolated from the tuber of Icacina trichantha. Their structures were elucidated based on spectroscopic and HRMS data. The absolute configurations of 1 and 5 were determined by single-crystal X-ray diffraction, and that of 2 was established by electronic circular dichroism data analysis. Compound 3 possesses a unique C-20 acetal moiety. This is the first report of the isolation of di-nor-(9ß-H)-pimarane derivatives from Icacina plants. Compounds 5 and 6 showed moderate cytotoxicity against MDA-MB-435, MDA-MB-231, and OVCAR3 cell lines, with IC50 values of 2.91-7.60 and 1.48-3.23 µM, respectively.
Asunto(s)
Abietanos/aislamiento & purificación , Magnoliopsida/química , Abietanos/química , Abietanos/farmacología , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Tubérculos de la Planta/químicaRESUMEN
Extract from the cultured freshwater cf. Oscillatoria sp. UIC 10045 showed antiproliferative activity against HT-29 cell line. Bioassay-guided fractionation led to the isolation of two new cyclic lipopeptides, named trichormamides C (1) and D (2). The planar structures were determined by combined analyses of HRESIMS, Q-TOF ESIMS/MS, and 1D and 2D NMR spectra. The absolute configurations of the amino acid residues were assigned by advanced Marfey's analysis after partial and complete acid hydrolysis. Trichormamides C (1) is a cyclic undecapeptide and D (2) is a cyclic dodecapeptide, both containing a lipophilic ß-aminodecanoic acid residue. Trichormamide C (1) displayed antiproliferative activities against HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 1.7 and 1.0µM, respectively, as well as anti-Mycobacterium tuberculosis activity with MIC value of 23.8µg/mL (17.3µM). Trichormamide D (2) was found to be less potent against both HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 11.5 and 11.7µM, respectively.
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Antibacterianos/química , Antineoplásicos/química , Cianobacterias/química , Lipopéptidos/química , Péptidos Cíclicos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Humanos , Concentración 50 Inhibidora , Lipopéptidos/aislamiento & purificación , Lipopéptidos/farmacología , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/crecimiento & desarrollo , Péptidos Cíclicos/aislamiento & purificación , Péptidos Cíclicos/farmacología , Relación Estructura-ActividadRESUMEN
Eight new and 10 known compounds were isolated from an organic extract of the bulbs of Bellevalia eigii as part of a search for anticancer leads from native plants of Jordan. Of these, the series of 16 homoisoflavonoids (1-16) comprise the seven new analogues 7-O-methyl-3'-hydroxy-3,9-dihydropunctatin (3), 6-hydroxy-7-O-methyl-3,9-dihydropunctatin (6), 7,4'-di-O-methyl-3'-hydroxy-3,9-dihydropunctatin (9), 7-O-methylpunctatin (10), 7-O-methyl-3'-hydroxypunctatin (13), 5-hydroxy-7,8-dimethoxychroman-4-one (14), and 7-O-methyl-8-demethoxy-3-hydroxy-3,9-dihydropunctatin (15). The known ferulic acid-derived acrylamide (17) and the new methylthioacrylate bellegimycin (18) are also reported. The structures were elucidated using a set of spectroscopic and spectrometric techniques; the absolute configurations of compounds 1-9, 15, and 16 were determined using ECD spectroscopy, while a modified Mosher's ester method was used for compound 18. Optical rotation data for the known compounds 1, 2, and 8 are reported here for the first time. The cytotoxic activities of all compounds were evaluated using the MDA-MB-435 (melanoma) and HT-29 (colon) cancer cell lines. Compounds 4 and 9 were the most potent on the latter cell line, with IC50 values of 1.0 and 1.1 µM, respectively. Compounds 1-18 were assessed for antimicrobial activity using a collection of bacteria and fungi; compounds 4 and 12 showed promising activity against the bacterium Mycobacterium smegmatis with MIC values of 17 and 24 µg/mL, respectively.
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Isoflavonas/aislamiento & purificación , Isoflavonas/farmacología , Liliaceae/química , Raíces de Plantas/química , Células HT29 , Humanos , Concentración 50 Inhibidora , Isoflavonas/química , Jordania , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Mycobacterium/efectos de los fármacos , Mycobacterium smegmatis/efectos de los fármacos , Resonancia Magnética Nuclear Biomolecular , Relación Estructura-Actividad , Vinblastina/farmacologíaRESUMEN
New 17-nor-pimaranes (1, 2), (9ßH)-pimaranes (3, 4), and 17-nor-(9ßH)-pimarane (5) were isolated from the tuber of Icacina trichantha. The structures were elucidated based on spectroscopic and HRMS data. The absolute configurations of 3 and 5 were determined by single-crystal X-ray diffraction. Compound 5 possesses a unique 19,20-δ-lactone moiety. Compound 3 showed cytotoxicity against MDA-MB-435 (human melanoma cancer) cells with an IC50 value of 7.04 µM. A plausible biogenetic pathway for compounds 1-5 is proposed.
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Abietanos/aislamiento & purificación , Magnoliopsida/química , Abietanos/química , Cristalografía por Rayos X , Humanos , Estructura Molecular , Nigeria , Resonancia Magnética Nuclear Biomolecular , Tubérculos de la Planta/químicaRESUMEN
Seven new 17-norpimarane and (9ßH)-17-norpimarane diterpenoids, icacinlactones A-G (1-7), were isolated from the tuber of Icacina trichantha. The structures were elucidated by spectroscopic and HRMS techniques, and the absolute configuration of 2 was determined by means of X-ray crystallographic analysis. Compounds 1-7, as well as four known related structures, were evaluated for cytotoxic activity against MDA-MB-435 (human melanoma cancer), MDA-MB-231 (human breast cancer), and OVCAR3 (human ovarian cancer) cell lines. Several of these natural products displayed significant cytotoxic activity, with humirianthenolide C being the most active.
Asunto(s)
Abietanos/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Magnoliopsida/química , Abietanos/química , Abietanos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Conformación Molecular , Estructura Molecular , Nigeria , Resonancia Magnética Nuclear Biomolecular , Tubérculos de la Planta/químicaRESUMEN
Fourteen new resorcylic acid lactones (1-14) were isolated from an organic extract of a culture of a freshwater aquatic fungus Halenospora sp. originating from a stream in North Carolina. The structures were elucidated using a set of spectroscopic and spectrometric techniques. The absolute configuration of one representative member of the compounds (7) was assigned using X-ray crystallography of an analogue that incorporated a heavy atom, whereas for compounds 8-11, a modified Mosher's ester method was utilized. The relative configurations of compounds 12-14 were determined on the basis of NOE data. Compounds 12-14 were proposed as artifacts produced by intramolecular cycloetherification of the ε-hydroxy-α,ß-unsaturated ketone moieties of the parent compounds during the purification processes. The isolated compounds, except for 8 and 12, were tested against the MDA-MB-435 (melanoma) and HT-29 (colon) cancer cell lines. Compound 5 was the most potent, with IC50 values of 2.9 and 7.5 µM, respectively. The compounds were evaluated as TAK1-TAB1 inhibitors but were found to be inactive.
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Antineoplásicos/aislamiento & purificación , Ascomicetos/química , Lactonas/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/farmacología , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Agua Dulce , Células HT29 , Humanos , Concentración 50 Inhibidora , Lactonas/química , Lactonas/farmacología , Conformación Molecular , Estructura Molecular , North Carolina , Resonancia Magnética Nuclear BiomolecularRESUMEN
Two new cyclic lipopeptides, trichormamides A (1) and B (2), were isolated from the cultured freshwater cyanobacterium Trichormus sp. UIC 10339. The strain was obtained from a sample collected in Raven Lake in Northern Wisconsin. The planar structures of trichormamides A (1) and B (2) were determined using a combination of spectroscopic analyses including HRESIMS and 1D and 2D NMR experiments. The absolute configurations of the amino acid residues were assigned by the advanced Marfey's method after acid hydrolysis. Trichormamide A (1) is a cyclic undecapeptide containing two D-amino acid residues (D-Tyr and D-Leu) and one ß-amino acid residue (ß-aminodecanoic acid). Trichormamide B (2) is a cyclic dodecapeptide characterized by the presence of four nonstandard α-amino acid residues (homoserine, N-methylisoleucine, and two 3-hydroxyleucines) and one ß-amino acid residue (ß-aminodecanoic acid). Trichormamide B (2) was cytotoxic against MDA-MB-435 and HT-29 cancer cell lines with IC50 values of 0.8 and 1.5 µM, respectively.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Cianobacterias/química , Agua Dulce/microbiología , Lipopéptidos/aislamiento & purificación , Lipopéptidos/farmacología , Péptidos Cíclicos/aislamiento & purificación , Péptidos Cíclicos/farmacología , Aminoácidos/química , Antineoplásicos/química , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Humanos , Concentración 50 Inhibidora , Lipopéptidos/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Péptidos Cíclicos/química , WisconsinRESUMEN
Two new (1 and 2) and three known (3-5) carbamidocyclophanes were isolated from a cultured freshwater cyanobacterium Nostoc sp. (UIC 10274) obtained from a sample collected at Des Plaines, Illinois. Their planar structures and stereoconfigurations were determined by extensive spectroscopic analysis including 1D/2D NMR experiments, HRESIMS as well as CD spectroscopy. Carbamidocyclophane F (1) showed potent anti-Mycobacterium tuberculosis activity in the microplate Alamar blue assay and low-oxygen-recovery assay with MIC values of 0.8 and 5.4 µM, respectively. Carbamidocyclophane F (1) also displayed antimicrobial activities against the gram positive bacteria Staphylococcus aureus and Enterococcus faecalis with MIC values of 0.1 and 0.2 µM, respectively. Carbamidocyclophane F (1) and Carbamidocyclophane G (2) both showed antiproliferative activity against MDA-MB-435 and HT-29 human cancer cell lines with IC50 values in the range from 0.5 to 0.7 µM.
RESUMEN
Three (9ßH)-pimaranes, 1, 2, and 3, and two (9ßH)-17-norpimaranes, 4 and 5, belonging to a rare compound class in nature, were obtained from the tubers of Icacina trichantha for the first time. Compound 1 is a new natural product, and 2-5 have been previously reported. The structures were elucidated based on NMR and MS data, and optical rotation values. The absolute configurations of (9ßH)-pimaranes were unambiguously established based on X-ray crystallographic analysis. Full NMR signal assignments for the known compounds 2, 4, and 5, which were not available in previous publications, are also reported. All five isolates displayed cytotoxic activities on MDA-MB-435 cells (IC50 0.66-6.44â µM), while 2, 3, and 4 also exhibited cytotoxicities on HT-29 cells (IC50 3.00-4.94â µM).
Asunto(s)
Abietanos/aislamiento & purificación , Diterpenos/aislamiento & purificación , Magnoliopsida/química , Abietanos/farmacología , Línea Celular Tumoral , Diterpenos/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Difracción de Rayos XRESUMEN
This study evaluated the aerosol exposure risks while using common noninvasive oxygenation devices. A simulated mannequin was designed to breathe at a minute ventilation of 20 L/min and used the following oxygen-therapy devices: nasal cannula oxygenation (NCO) at 4 and 15 L/min, nonrebreathing mask (NRM) at 15 L/min, simple mask at 6 L/min, combination of NCO at 15 L/min and NRM at 15 L/min, high-flow nasal cannula (HFNC) at 50 L/min, and flush rate NRM. Two-dimension of the dispersion distance and the aerosol concentrations were measured at head, trunk, and foot around the mannequin for over 10 min. HFNC and flush-rate NRM yielded the longest dispersion distance and highest aerosol concentrations over the three sites of the mannequin than the other oxygenation devices and should use with caution. For flow rates of < 15 L/min, oxygenation devices with mask-like effects, such as NRM or NCO with NRM, decreased aerosol dispersion more effectively than NCO alone or a simple mask. In the upright position, the foot area exhibited the highest aerosol concentration regardless of the oxygenation device than the head-trunk areas of the mannequin. Healthcare workers should be alert even at the foot side of the patient while administering oxygenation therapy.
Asunto(s)
Terapia por Inhalación de Oxígeno , Humo , Humanos , Aerosoles , Terapia por Inhalación de Oxígeno/métodos , Pulmón , Administración por InhalaciónRESUMEN
To evaluate aerosol exposure risk and prevention strategies during bystander, pre-hospital, and inpatient cardiopulmonary resuscitation (CPR). This study compared hands-only CPR, CPR with a surgical or N95 mask, and CPR with a non-rebreather mask at 15 L/min. 30:2 compression-ventilation ratio CPR was tested with face-mask ventilation (FMV), FMV with a high efficiency particulate air (HEPA) filter; supraglottic airway (SGA), SGA with a surgical mask, SGA with a HEPA filter, or SGA with both. Continuous CPR was tested with an endotracheal tube (ET), ET with a surgical mask, a HEPA filter, or both. Aerosol concentration at the head, trunk, and feet of the mannequin were measured to evaluate exposure to CPR personnel. Hands-only CPR with a surgical or N95 face mask coverings and ET tube ventilation CPR with filters showed the lowest aerosol exposure among all study groups, including CPR with NRM oxygenation, FMV, and SGA ventilation. NRM had a mask effect and reduced aerosol exposure at the head, trunk, and feet of the mannequin. FMV with filters during 30:2 CPR reduced aerosol exposure at the head and trunk, but increased at the feet of the mannequin. A tightly-sealed SGA when used with a HEPA filter, reduced aerosol exposure by 21.00-63.14% compared with a loose-fitting one. Hands-only CPR with a proper fit surgical or N95 face mask coverings is as safe as ET tube ventilation CPR with filters, compared with CPR with NRM, FMV, and SGA. FMV or tight-sealed SGA ventilation with filters prolonged the duration to achieve estimated infective dose of SARS-CoV-2 2.4-2.5 times longer than hands-on CPR only. However, a loose-fitting SGA is not protective at all to chest compressor or health workers standing at the foot side of the victim, so should be used with caution even when using with HEPA filters.
Asunto(s)
COVID-19 , Reanimación Cardiopulmonar , Humanos , Maniquíes , Pacientes Internos , COVID-19/prevención & control , SARS-CoV-2 , Aerosoles y Gotitas Respiratorias , Intubación Intratraqueal , HospitalesRESUMEN
A quantitative phase shifting differential interference contrast (PS-DIC) shearing interferometer is adopted to measure the profile of transparent specimen with inclined surface. The effects of the incline angle on DIC measurement accuracy were studied. The optical model of the test system was constructed and the measurement of surface with various incline angles ranging from 5° to 60° was simulated. The experiments validate the simulation model and show the feasibility of profile reconstruction of inclined structure. It is interested to find that even with an inclined angle of 15°, unwrapping technique is required to make the measurement more accurate. In addition, the measurement can be further improved by taking into account the effects of the change in shear distance on the optical path difference. This study provides useful information that should be considered for complex geometry measurement with quantitative DIC technique.