RESUMEN
In recent years, commercial air transport has increased considerably. However, the compositions and source profiles of volatile organic compounds (VOCs) emitted from aircraft are still not clear. In this study, the characteristics of VOCs (including oxygenated VOCs (OVOCs)) emitted from airport sources were measured at Shenzhen Bao'an International Airport. The results showed that the compositions and proportions of VOC species showed significant differences as the aircraft operating state changed. OVOCs were the dominant species and accounted for 63.17%, 58.44%, and 51.60% of the total VOC mass concentration during the taxiing, approach, and take-off stages. Propionaldehyde and acetone were the main OVOCs, and dichloromethane and 1,2-dichloroethane were the main halohydrocarbons. Propane had the highest proportion among all alkanes, while toluene and benzene were the predominant aromatic hydrocarbons. Compared with the source profiles of VOCs from construction machinery, the proportions of halogenated hydrocarbons and alkanes emitted from aircraft were significantly higher, as were those of propionaldehyde and acetone. OVOCs were still the dominant VOC species in aircraft emissions, and their calculated ozone formation potential (OFP) was much higher than that of other VOC species at all stages of aircraft operations. Acetone, propionaldehyde, formaldehyde, acetaldehyde, and ethylene were the greatest contributors to ozone production. This study comprehensively measured the distribution characteristics of VOCs, and its results will aid in the construction of a source profile inventory of VOCs emitted from aircraft sources in real atmospheric environments.
RESUMEN
Severe emerging and re-emerging viral infections such as Lassa fever, Avian influenza (AI), and COVID-19 caused by SARS-CoV-2 urgently call for new strategies for the development of broad-spectrum antivirals targeting conserved components in the virus life cycle. Viral lipids are essential components, and viral-cell membrane fusion is the required entry step for most unrelated enveloped viruses. In this paper, we identified a porphyrin derivative of protoporphyrin IX (PPIX) that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses including Lassa virus (LASV), Machupo virus (MACV), and SARS-CoV-2 as well as various subtypes of influenza A viral strains with IC50 values ranging from 0.91 ± 0.25 µM to 1.88 ± 0.34 µM. A mechanistic study using influenza A/Puerto Rico/8/34 (H1N1) as a testing strain showed that PPIX inhibits the infection in the early stage of virus entry through biophysically interacting with the hydrophobic lipids of enveloped virions, thereby inhibiting the entry of enveloped viruses into host cells. In addition, the preliminary antiviral activities of PPIX were further assessed by testing mice infected with the influenza A/Puerto Rico/8/34 (H1N1) virus. The results showed that compared with the control group without drug treatment, the survival rate and mean survival time of the mice treated with PPIX were apparently prolonged. These data encourage us to conduct further investigations using PPIX as a lead compound for the rational design of lipid-targeting antivirals for the treatment of infection with enveloped viruses.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Protoporfirinas/uso terapéutico , Internalización del Virus/efectos de los fármacos , Animales , Antivirales/síntesis química , Antivirales/metabolismo , Antivirales/farmacología , Arenavirus del Nuevo Mundo/efectos de los fármacos , Chlorocebus aethiops , Perros , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Virus Lassa/efectos de los fármacos , Células de Riñón Canino Madin Darby , Masculino , Lípidos de la Membrana/metabolismo , Ratones , Pruebas de Sensibilidad Microbiana , Protoporfirinas/síntesis química , Protoporfirinas/metabolismo , Protoporfirinas/farmacología , SARS-CoV-2/efectos de los fármacos , Células Vero , Envoltura Viral/efectos de los fármacosRESUMEN
Marine environments are known to be a new source of structurally diverse bioactive molecules. In this paper, we identified a porphyrin derivative of Pyropheophorbide a (PPa) from the mussel Musculus senhousei (M. senhousei) that showed broad anti-influenza A virus activity in vitro against a panel of influenza A viral strains. The analysis of the mechanism of action indicated that PPa functions in the early stage of virus infection by interacting with the lipid bilayer of the virion, resulting in an alteration of membrane-associated functions, thereby blocking the entry of enveloped viruses into host cells. In addition, the anti-influenza A virus activity of PPa was further assessed in mice infected with the influenza A virus. The survival rate and mean survival time of mice were apparently prolonged compared with the control group which was not treated with the drug. Therefore, PPa and its derivatives may represent lead compounds for controlling influenza A virus infection.
Asunto(s)
Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Bivalvos/química , Clorofila/análogos & derivados , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Virus Sincitiales Respiratorios/efectos de los fármacos , Virión/efectos de los fármacos , Animales , Antivirales/química , Antivirales/aislamiento & purificación , Betacoronavirus/crecimiento & desarrollo , Betacoronavirus/metabolismo , Clorofila/química , Clorofila/aislamiento & purificación , Clorofila/farmacología , Perros , Interacciones Huésped-Patógeno/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/crecimiento & desarrollo , Subtipo H1N1 del Virus de la Influenza A/metabolismo , Membrana Dobles de Lípidos/antagonistas & inhibidores , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/metabolismo , Células de Riñón Canino Madin Darby , Masculino , Ratones , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/mortalidad , Infecciones por Orthomyxoviridae/patología , Infecciones por Orthomyxoviridae/virología , Virus Sincitiales Respiratorios/crecimiento & desarrollo , Virus Sincitiales Respiratorios/metabolismo , SARS-CoV-2 , Alimentos Marinos , Análisis de Supervivencia , Virión/crecimiento & desarrollo , Virión/metabolismo , Internalización del Virus/efectos de los fármacosRESUMEN
Actinobacteria are historically and continued to be an important source for drug discovery. The annual epidemics and periodic pandemics of humans induced by influenza A virus (IAV) prompted us to develop new effective antiviral drugs with different modes of action. An actinobacterium of Streptomyces sp. SMU 03 was identified from the feces of Elephas maximus in Yunnan Province, China. By employing an H5N1 pseudo-typed virus drug screening system, the anti-IAV effect of the dichloromethane extracts (DCME) of this bacterium was investigated. DCME showed broad and potent activities against several influenza viruses, including the H1N1 and H3N2 subtypes and influenza B virus, with IC50 values ranging from 0.37 ± 0.22 to 14.44 ± 0.79 µg/mL. A detailed modes-of-action study indicated that DCME might interact with the HA2 subunit of hemagglutinin (HA) of IAV by interrupting the fusion process between the viral and host cells' membranes thereby inhibiting the entry of the virus into host cells. Furthermore, the in vivo anti-IAV activity test of DCME showed that compared with the no-drug treated group, the survival rates, appearances, weights, lung indices and histopathological changes were all significantly alleviated. Based on these results, the chemical constituent study of DCME was then investigated, from which a number of antiviral compounds with various structural skeletons have been isolated and identified. Overall, these data indicated that the DCME from Streptomyces sp. SMU 03 might represent a good source for antiviral compounds that can be developed as potential antivirus remedies.
Asunto(s)
Antivirales/farmacología , Elefantes/microbiología , Streptomyces/química , Animales , Antivirales/aislamiento & purificación , China , Perros , Heces/microbiología , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H5N1 del Virus de la Influenza A/efectos de los fármacos , Células de Riñón Canino Madin Darby , Ratones Endogámicos BALB C , Estructura Molecular , Streptomyces/aislamiento & purificaciónRESUMEN
BACKGROUND AND PURPOSE: Propionibacterium acnes is a Gram-positive bacterium associated with the skin disorder acne. In this study, as fatty acids are considered to be important in the life habitat of P. acnes, we tested our lipopeptide library in an attempt to create potent P. acnes-specific antimicrobial agents. EXPERIMENTAL APPROACH: The antimicrobial activity of various lipopeptides was determined by measuring their minimal inhibitory concentration (MIC). Lipids from P. acnes were used to explore their mode of action. RAW264.7 cells stimulated with LPS and P. acnes respectively were used to measure their anti-inflammatory activity. Mice ears injected with P. acnes were used to assess the antimicrobial and anti-inflammatory effects of the peptides tested in vivo. KEY RESULTS: The most potent candidate, C16-KWKW, was observed to be more active against P. acnes than against other non-targeted bacterial strains, such as Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The mode of action of C16-KWKW was observed to be through interference with the integrity of the bacterial membrane, thereby impairing membrane permeability and causing leakage of inner contents of bacterial cells. Furthermore, C16-KWKW inhibited the expression of pro-inflammatory cytokines, such as IL-1ß, TNF-α, and inducible NOS stimulated by both LPS and P. acnes, thus showing potential anti-inflammatory activity, which was further verified in the in vivo animal studies. CONCLUSIONS AND IMPLICATIONS: C16-KWKW is a lipopeptide displaying both anti-P. acnes and anti-inflammatory effects in vitro and in vivo and shows potential as a treatment for acne vulgaris induced by P. acnes.
Asunto(s)
Antibacterianos/farmacología , Antiinflamatorios/farmacología , Lipopéptidos/farmacología , Propionibacterium acnes/efectos de los fármacos , Acné Vulgar/tratamiento farmacológico , Animales , Línea Celular , Ciclooxigenasa 2/genética , Femenino , Humanos , Interleucina-1beta/genética , Ratones , Pruebas de Sensibilidad Microbiana , FN-kappa B/genética , Óxido Nítrico Sintasa de Tipo II/genética , Propionibacterium acnes/crecimiento & desarrollo , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Dental plaque is closely related to the occurrence of dental caries, of which the main causative bacterium is Streptococcus mutans (S. mutans). In this study, to create potent antibiofilm agents, we chose a human antimicrobial peptide LL-37 as our starting material and modified it by cutting it shorter and varying its charge and hydrophobicity. The results of anti-S. mutans as well as biofilm inhibitory activity tests indicated that two derivatives, IG-13-1 and IG-13-2, were the most potent one toward both planktonic and biofilm S. mutans cells with the minimal inhibitory concentration of 5.0 µM and minimal biofilm inhibitory concentrations of 5.91 ± 0.91 µM and 7.58 ± 0.23 µM, respectively. The modes of action study showed that IG-13-1 and IG-13-2 were functioned by disrupting the bacterial membrane, causing the leakage of inner contents, thereby leading to the death of bacterial cells eventually. In addition, IG-13-1 and IG-13-2 were able to suppress the expression of proinflammatory cytokine of TNF-α and reduce the level of nuclear transcription factor-κB, which indicated the potential anti-inflammatory activity of these peptides. Conclusively, this study indicated that IG-13-1 and IG-13-2 are potent peptides in both anti-S. mutans and anti-inflammatory activities, therefore, showing a potential application for the prevention and treatment of dental caries.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/farmacología , Biopelículas/efectos de los fármacos , Diseño de Fármacos , Mutación , Streptococcus mutans/efectos de los fármacos , Secuencia de Aminoácidos , Animales , Membrana Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ratones , Pruebas de Sensibilidad Microbiana , FN-kappa B , Células RAW 264.7 , Streptococcus mutans/genética , Streptococcus mutans/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , CatelicidinasRESUMEN
BACKGROUND AND PURPOSE: Propionibacterium acnes (P. acnes) is a Gram-positive bacterium associated with the skin disorder acne. In this study, we determined the importance of fatty acids in the life habitat of P. acnes; we tested our lipopeptide library in an attempt to create potent P. acnes-specific antimicrobial agents. EXPERIMENTAL APPROACH: Antimicrobial activity was determined by the minimal inhibitory concentration (MIC). Lipids from P. acnes were used to explore the mode of action. RAW264.7 cells respectively stimulated with LPS and P. acnes were used to measure the anti-inflammatory activity. Mice ears injected with P. acnes were used to assess the antimicrobial and anti-inflammatory effects of the peptides tested in vivo. KEY RESULTS: The most potent candidate, C16-KWKW, was observed to be more active against P. acnes, with an MIC of 2 µg·ml-1 , than against other non-targeted bacterial strains, such as Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The mode of action of C16-KWKW was observed to be through interference with the integrity of bacterial membrane, thereby impairing membrane permeability and causing leakage of the inner contents of bacterial cells. In addition, C16-KWKW inhibited the expression of pro-inflammatory cytokines, such as IL-1ß, TNF-α, and inducible NOS, stimulated by both LPS and P. acnes, thus showing potential anti-inflammatory activity, which was further assessed in animal studies in vivo. CONCLUSIONS AND IMPLICATIONS: C16-KWKW is a lipopeptide displaying both anti-P. acnes and anti-inflammatory effects in vitro and in vivo, and exhibits potential as a treatment for acne vulgaris induced by P. acnes.
RESUMEN
Actinobacteria are a phylum of bacteria known for their potential in producing structurally diversified natural products that are always associated with a broad range of biological activities. In this paper, using an H5N1 pseudo-typed virus drug screening system combined with a bioassay guided purification approach, an antiviral butanolide (1) was identified from the culture broth of Streptomyces sp. SMU03, a bacterium isolated from the feces of Elephas maximus in Yunnan province, China. This compound displayed broad and potent activity against a panel of influenza viruses including H1N1 and H3N2 subtypes, as well as influenza B virus and clinical isolates with half maximal inhibitory concentration values (IC50) in the range of 0.29 to 12 µg/mL. In addition, 1 was also active against oseltamivir-resistant influenza virus strain of A/PR/8/34 with NA-H274Y mutation. Studies on the detailed modes of action suggested that 1 functioned by interfering with the fusogenic process of hemagglutinin (HA) of influenza A virus (IAV), thereby blocking the entry of virus into host cells. Furthermore, the anti-IAV activity of 1 was assessed with infected BALB/c mice, of which the appearance, weight, and histopathological changes in the infected lungs were significantly alleviated compared with the no-drug-treated group. Conclusively, these results provide evidence that natural products derived from microbes residing in animal intestines might be a good source for antiviral drug discovery.
Asunto(s)
4-Butirolactona/análogos & derivados , Antivirales/farmacología , Virus de la Influenza A/efectos de los fármacos , Intestinos/efectos de los fármacos , Infecciones por Orthomyxoviridae/virología , Streptomyces/metabolismo , 4-Butirolactona/química , 4-Butirolactona/farmacología , Animales , Antivirales/química , Línea Celular , Efecto Citopatogénico Viral , Elefantes , Activación Enzimática/efectos de los fármacos , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Concentración 50 Inhibidora , Masculino , Ratones , Neuraminidasa/metabolismoRESUMEN
Influenza A viruses (IAVs) induce acute respiratory disease and cause significant morbidity and mortality throughout the world. With the emergence of drug-resistant viral strains, new and effective anti-IAV drugs with different modes of action are urgently needed. In this study, by conjugating cholesterol to the N-terminus of the short peptide KKWK, a lipopeptide named S-KKWK was created. The anti-IAV test indicated that S-KKWK and its derivatives displayed potent antiviral activities against a broad variety of influenza A viral strains including oseltamivir-resistant strains and clinically relevant isolates with IC50 values ranging from 0.7 to 3.0µM. An extensive mechanistic study showed that these peptides functioned as viral "entry blockers" by inhibiting the conformational rearrangements of HA2 subunit, thereby interrupting the fusion of virus-host cell membranes. Significantly, a computer-aided docking simulation and protein sequence alignment identified conserved residues in the stem region of HA2 as the possible binding site of S-KKWK, which may be employed as a potential drug target for designing anti-IAVs with a broad-spectrum of activity. By targeting this region, a potent anti-IAV agent was subsequently created. In addition, the anti-IAV activity of S-KKWK was assessed by experiments with influenza A virus-infected mice, in which S-KKWK reduced the mortality of infected animals and extended survival time significantly. Overall, in addition to providing a strategy for designing broad-spectrum anti-IAV agents, these results indicate that S-KKWK and its derivatives are prospective candidates for potent antivirals.
Asunto(s)
Antivirales/metabolismo , Secuencia Conservada/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Hemaglutininas/metabolismo , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/metabolismo , Internalización del Virus/efectos de los fármacos , Secuencia de Aminoácidos , Animales , Antivirales/administración & dosificación , Pollos , Secuencia Conservada/fisiología , Perros , Hemaglutininas/genética , Humanos , Virus de la Influenza A/genética , Células de Riñón Canino Madin Darby , Masculino , Ratones , Ratones Endogámicos BALB C , Estructura Secundaria de Proteína , Estructura Terciaria de ProteínaRESUMEN
OBJECTIVES: In the past decade, the mobile phone (MP) has become extremely popular among children and the average age at which children own their first MP has decreased. The potential health effects of children's exposure to MP have been the subject of widespread public concern. The aim of our study is to investigate the associations between MP use and well-being in children. DESIGN: Cross-sectional study. SETTING: The questionnaires were completed in class with items regarding demographics, MP usage, self-reported well-being (symptoms were taken from the questionnaire of the HBSC survey) and possible confounding factors between October 2011 and May 2012 in Chongqing, China. Data were analysed using χ(2) tests and logistic regression models. PARTICIPANTS: Among the 793 children invited to participate, 781 returned the questionnaires. RESULTS: In total, 746 (94.1%) valid questionnaires were received. Fatigue was significantly associated with the years of MP usage (OR 1.85; 95% CI 1.07 to 3.22) and the daily duration of MP calls (OR 2.98; 95% CI 1.46 to 6.12). Headache was significantly associated with the daily duration of MP calls (OR 2.85; 95% CI 1.23 to 6.57). However, after adjusting for confounders only, the association between fatigue and MP usage remained statistically significant. There was no significant association between MP use and other physical symptoms in children. CONCLUSIONS: The present study indicated that there was a consistent significant association between MP use and fatigue in children. Further in-depth research is needed to explore the potential health effects of MP use in children.