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1.
J Cell Biochem ; 125(6): e30566, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38591648

RESUMEN

We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m-2) or obese (OB BMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.


Asunto(s)
Autopsia , COVID-19 , Metaboloma , Obesidad , Humanos , COVID-19/metabolismo , COVID-19/mortalidad , COVID-19/patología , COVID-19/virología , Obesidad/metabolismo , Obesidad/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , SARS-CoV-2/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Metabolómica/métodos , Índice de Masa Corporal , Adulto , Estrés Oxidativo , Interleucina-6/metabolismo
2.
Fitoterapia ; 173: 105810, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38163448

RESUMEN

Ent-hardwickiic acid is the major compound of Copaifera pubiflora Benth oleoresin traditionally used in Brazilian folk medicine as an antimicrobial agent. Microbial transformation of ent-hardwickiic by Cunninghamella elegans ATCC 10028b resulted in two and five antifungal derivatives (four new ones) produced in the Czapek modified and Koch's K1 media, respectively. The derivatives were isolated and their structures were determined by spectral analysis, namely 1D/2D NMR and HR-ESIMS. All compounds were tested for cytotoxic and antifungal activities and they were not cytotoxic to the tested cell lines, but all derivatives showed fungicidal activity against Candida glabrata and Candida krusei, which have emerged as resistant to fluconazole. One of the yet unreported biotransformation products displayed the strongest activity with minimum fungicidal concentration values smaller than the other compounds, including fluconazole.


Asunto(s)
Antifúngicos , Diterpenos , Fluconazol , Fluconazol/farmacología , Candida , Estructura Molecular , Pruebas de Sensibilidad Microbiana
3.
Appl Microbiol Biotechnol ; 108(1): 112, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38217254

RESUMEN

Marine bacteria living in association with marine sponges have proven to be a reliable source of biologically active secondary metabolites. However, no studies have yet reported natural products from Microbacterium testaceum spp. We herein report the isolation of a M. testaceum strain from the sponge Tedania brasiliensis. Molecular networking analysis of bioactive pre-fractionated extracts from culture media of M. testaceum enabled the discovery of testacosides A-D. Analysis of spectroscopic data and chemical derivatizations allowed the identification of testacosides A-D as glycoglycerolipids bearing a 1-[α-glucopyranosyl-(1 → 3)-(α-mannopyranosyl)]-glycerol moiety connected to 12-methyltetradecanoic acid for testacoside A (1), 14-methylpentadecanoic acid for testacoside B (2), and 14-methylhexadecanoic acid for testacosides C (3) and D (4). The absolute configuration of the monosaccharide residues was determined by 1H-NMR analysis of the respective diastereomeric thiazolidine derivatives. This is the first report of natural products isolated from cultures of M. testaceum. KEY POINTS: • The first report of metabolites produced by Microbacterium testaceum. • 1-[α-Glucopyranosyl-(1 → 3)-(α-mannopyranosyl)]-glycerol lipids isolated and identified. • Microbacterium testaceum strain isolated from the sponge Tedania brasiliensis.


Asunto(s)
Actinomycetales , Productos Biológicos , Glucolípidos , Poríferos , Animales , Glicerol/metabolismo , Poríferos/química , Actinomycetales/metabolismo , Espectroscopía de Resonancia Magnética , Productos Biológicos/metabolismo , Microbacterium
4.
Int J Mol Sci ; 24(23)2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-38069087

RESUMEN

Inspiratory muscle training (IMT) is known to promote physiological benefits and improve physical performance in endurance sports activities. However, the metabolic adaptations promoted by different IMT prescribing strategies remain unclear. In this work, a longitudinal, randomized, double-blind, sham-controlled, parallel trial was performed to investigate the effects of 11 weeks (3 days·week-1) of IMT at different exercise intensities on the serum metabolomics profile and its main regulated metabolic pathways. Twenty-eight healthy male recreational cyclists (30.4 ± 6.5 years) were randomized into three groups: sham (6 cm·H2O of inspiratory pressure, n = 7), moderate-intensity (MI group, 60% maximal inspiratory pressure (MIP), n = 11) and high-intensity (HI group, 85-90% MIP, n = 10). Blood serum samples were collected before and after 11 weeks of IMT and analyzed by 1H NMR and UHPLC-HRMS/MS. Data were analyzed using linear mixed models and metabolite set enrichment analysis. The 1H NMR and UHPLC-HRMS/MS techniques resulted in 46 and 200 compounds, respectively. These results showed that ketone body metabolism, fatty acid biosynthesis, and aminoacyl-tRNA biosynthesis were upregulated after IMT, while alpha linolenic acid and linoleic acid metabolism as well as biosynthesis of unsaturated fatty acids were downregulated. The MI group presented higher MIP, Tryptophan, and Valine levels but decreased 2-Hydroxybutyrate levels when compared to the other two studied groups. These results suggest an increase in the oxidative metabolic processes after IMT at different intensities with additional evidence for the upregulation of essential amino acid metabolism in the MI group accompanied by greater improvement in respiratory muscle strength.


Asunto(s)
Ejercicios Respiratorios , Suero , Humanos , Masculino , Ejercicios Respiratorios/métodos , Cromatografía Líquida de Alta Presión , Fuerza Muscular/fisiología , Espectroscopía de Protones por Resonancia Magnética , Músculos Respiratorios , Estudios Longitudinales
5.
Fitoterapia ; 171: 105686, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37748714

RESUMEN

The chemical composition of V. pyrantha resin (VpR) and fractions (VpFr1-7 and VpWS) were assessed by LC-MS and NMR. Twenty-eight metabolites were identified, including 16 diterpenoids, seven nor-diterpenoids, one fatty acid, one bis-diterpenoid, one steroid, one flavonoid, and one triterpenoid. The pharmacological potential of VpR, VpFr1-7, and isolated compounds was assessed by determining their antioxidant, antimicrobial, and cytotoxic activities. VpFr4 (IC50 = 205.48 ± 3.37 µg.mL-1) had the highest antioxidant activity, whereas VpFr6 (IC50 = 842.79 ± 10.23 µg.mL-1) had the lowest. The resin was only active against Staphylococcus aureus (MIC 62.5 µg.mL-1) and Salmonella choleraesius (MIC and MFC 500 µg.mL-1), but fractions were enriched with antibacterial compounds. V. pyrantha resin and fractions showed great cytotoxic activity against HCT116 (IC50 = 20.08 µg.mL-1), HepG2 (IC50 = 20.50 µg.mL-1), and B16-F10 (12.17 µg.mL-1) cell lines. Multivariate statistical analysis was used as a powerful tool to pinpoint possible metabolites responsible for the observed activities.


Asunto(s)
Antiinfecciosos , Antineoplásicos , Diterpenos , Extractos Vegetales/química , Estructura Molecular , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Diterpenos/farmacología
6.
J Nat Prod ; 86(8): 2065-2072, 2023 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-37490470

RESUMEN

Metabolomics analyses and improvement of growth conditions were applied toward diversification of phomactin terpenoids by the fungus Biatriospora sp. CBMAI 1333. Visualization of molecular networking results on Gephi assisted the observation of phomactin diversification and guided the isolation of new phomactin variants by applying a modified version of chemometrics based on a fractional factorial design. Consequentially, the first nitrogen-bearing phomactin, phomactinine (1), with a new rearranged carbon skeleton, was isolated and identified. The strategy combining metabolomics and chemometrics can be extended to include bioassay potency, structure novelty, and metabolic diversification connected or not to genomic analyses.


Asunto(s)
Ascomicetos , Ascomicetos/química , Estructura Molecular
8.
J Nat Prod ; 86(6): 1476-1486, 2023 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-37289832

RESUMEN

Bioassay-guided investigation of the EtOAc-soluble extract of a culture of the marine-derived fungus Peroneutypa sp. M16 led to the isolation of seven new polyketide- and terpenoid-derived metabolites (1, 2, 4-8), along with known polyketides (3, 9-13). Structures of compounds 1, 2, and 4-8 were established by analysis of spectroscopic data. Absolute configurations of compounds 1, 2, 4, 6, 7, and 8 were determined by the comparison of experimental ECD spectra with calculated CD data. Compound 5 exhibited moderate antiplasmodial activity against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum.


Asunto(s)
Policétidos , Xylariales , Policétidos/química , Terpenos/química , Estructura Molecular , Extractos Vegetales
9.
Clin Chim Acta ; 539: 18-25, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36450311

RESUMEN

Individuals with sickle cell disease (SCD) often experience numerous vaso-occlusive crisis events throughout their lives, which can progress to severe damage of several organs, including avascular necrosis, also known as osteonecrosis (ON). Osteonecrosis is one of the most devastating musculoskeletal clinical manifestations of sickle cell disease, afflicting up to 50% of the SCD patients. Herein, a NMR-based untargeted metabolomics approach was used to assess the metabolome alterations of blood plasma and bone marrow interstitial fluid (BMIF) samples of SCD patients with osteonecrosis. Furthermore, biochemical signatures associated with different osteonecrosis stages were assessed by analysing the metabolome of blood plasma and bone marrow interstitial fluid samples of SCD patients with different stages of the disease based on the Fiat and Arlet classification (FAC). Multivariate statistical analysis allowed a clear discrimination between the studied groups and it provided important insights into the different osteonecrosis stages. Citrate was pointed out as a possible biomarker to differentiate SCD patients with and without osteonecrosis. Acetate, creatinine, histidine, tyrosine, glucose, and NI5 seems to be key metabolites associated to different stages of the disease. Although this is a pioneer exploratory study, we acknowledge that fact that it is limited by the group sizes and absence of a validation cohort. Nevertheless, multivariate statistical analyses indicated that the metabolome of blood plasma and BMIF samples encompasses a complex metabolic regulation system for osteonecrosis.


Asunto(s)
Anemia de Células Falciformes , Osteonecrosis , Humanos , Líquido Extracelular , Médula Ósea , Metabolómica , Plasma
10.
Org Lett ; 24(51): 9381-9385, 2022 12 30.
Artículo en Inglés | MEDLINE | ID: mdl-36521009

RESUMEN

Comparative metabolomics analysis of nonphytotoxic endophytic Colletotrichum spp. isolated from Anthurium alcatrazense endemic to Alcatrazes island (Brazil) and phytopathogenic Colletotrichum spp. isolated from the mainland of Brazil revealed significant differences in chemical composition. Examination of endophytic Colletotrichum spp. from Alcatrazes island led to the discovery of a 26-member macrolactone, colletotrichumolide (1), containing a phosphatidyl choline side chain. Further examination of the phytopathogenic strains from the mainland identified a family of phytopathogenic metabolites not present in the nonpathogenic island-derived strains, suggesting that geographical isolation could influence the secondary metabolism of fungal strains.


Asunto(s)
Colletotrichum , Colletotrichum/química , Brasil , Metabolismo Secundario
11.
Molecules ; 27(24)2022 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-36557788

RESUMEN

Aging process is characterized by a progressive decline of several organic, physiological, and metabolic functions whose precise mechanism remains unclear. Metabolomics allows the identification of several metabolites and may contribute to clarifying the aging-regulated metabolic pathways. We aimed to investigate aging-related serum metabolic changes using a metabolomics approach. Fasting blood serum samples from 138 apparently healthy individuals (20−70 years old, 56% men) were analyzed by Proton Nuclear Magnetic Resonance spectroscopy (1H NMR) and Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS), and for clinical markers. Associations of the metabolic profile with age were explored via Correlations (r); Metabolite Set Enrichment Analysis; Multiple Linear Regression; and Aging Metabolism Breakpoint. The age increase was positively correlated (0.212 ≤ r ≤ 0.370, p < 0.05) with the clinical markers (total cholesterol, HDL, LDL, VLDL, triacylglyceride, and glucose levels); negatively correlated (−0.285 ≤ r ≤ −0.214, p < 0.05) with tryptophan, 3-hydroxyisobutyrate, asparagine, isoleucine, leucine, and valine levels, but positively (0.237 ≤ r ≤ 0.269, p < 0.05) with aspartate and ornithine levels. These metabolites resulted in three enriched pathways: valine, leucine, and isoleucine degradation, urea cycle, and ammonia recycling. Additionally, serum metabolic levels of 3-hydroxyisobutyrate, isoleucine, aspartate, and ornithine explained 27.3% of the age variation, with the aging metabolism breakpoint occurring after the third decade of life. These results indicate that the aging process is potentially associated with reduced serum branched-chain amino acid levels (especially after the third decade of life) and progressively increased levels of serum metabolites indicative of the urea cycle.


Asunto(s)
Ácido Aspártico , Isoleucina , Masculino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Femenino , Leucina , Metabolómica/métodos , Metaboloma/fisiología , Envejecimiento , Biomarcadores , Valina , Ornitina , Urea
12.
J Clin Virol Plus ; 2(3): 100101, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35959109

RESUMEN

There is a massive demand to identify alternative methods to detect new cases of COVID-19 as well as to investigate the epidemiology of the disease. In many countries, importation of commercial kits poses a significant impact on their testing capacity and increases the costs for the public health system. We have developed an ELISA to detect IgG antibodies against SARS-CoV-2 using a recombinant viral nucleocapsid (rN) protein expressed in E. coli. Using a total of 894 clinical samples we showed that the rN-ELISA was able to detect IgG antibodies against SARS-CoV-2 with high sensitivity (97.5%) and specificity (96.3%) when compared to a commercial antibody test. After three external validation studies, we showed that the test accuracy was higher than 90%. The rN-ELISA IgG kit constitutes a convenient and specific method for the large-scale determination of SARS-CoV-2 antibodies in human sera with high reliability.

13.
J Clin Virol Plus ; : 100103, 2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-35993012

RESUMEN

There is a massive demand to identify alternative methods to detect new cases of COVID-19 as well as to investigate the epidemiology of the disease. In many countries, importation of commercial kits poses a significant impact on their testing capacity and increases the costs for the public health system. We have developed an ELISA to detect IgG antibodies against SARS-CoV-2 using a recombinant viral nucleocapsid (rN) protein expressed in E. coli. Using a total of 894 clinical samples we showed that the rN-ELISA was able to detect IgG antibodies against SARS-CoV-2 with high sensitivity (97.5%) and specificity (96.3%) when compared to a commercial antibody test. After three external validation studies, we showed that the test accuracy was higher than 90%. The rN-ELISA IgG kit constitutes a convenient and specific method for the large-scale determination of SARS-CoV-2 antibodies in human sera with high reliability.

14.
J Nat Prod ; 85(5): 1340-1350, 2022 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-35427139

RESUMEN

Investigation of the marine sponge Agelas dispar MeOH fractions using feature-based molecular networking, dereplication, and isolation led to the discovery of new bromopyrrole-derived metabolites. An in-house library of bromopyrrole alkaloids previously isolated from A. dispar and Dictyonella sp. was utilized, along with the investigation of an MS/MS fragmentation of these compounds. Our strategy led to the isolation and identification of the disparamides A-C (1-3), with a novel carbon skeleton. Additionally, new dispyrins B-F (4-8) and nagelamides H2 and H3 (9 and 10) and known nagelamide H (11), citrinamine B (12), ageliferin (13), bromoageliferin (14), and dibromoageliferin (15) were also isolated and identified by analysis of spectroscopic data. Analysis of MS/MS fragmentation data and molecular networking analysis indicated the presence of hymenidin (16), oroidin (17), dispacamide (18), monobromodispacamide (19), keramadine (20), longamide B (21), methyl ester of longamide B (22), hanishin (23), methyl ester of 3-debromolongamide B (24), and 3-debromohanishin (25). Antibacterial activity of ageliferin (13), bromoageliferin (14), and dibromoageliferin (15) was evaluated against susceptible and multi-drug-resistant ESKAPE pathogenic bacteria Klabsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterococcus faecalis. Dibromoageliferin (15) displayed the most potent antimicrobial activity against all tested susceptible and MDR strains. Compounds 13-15 presented no significant hemolytic activity up to 100 µM.


Asunto(s)
Agelas , Alcaloides , Poríferos , Agelas/química , Alcaloides/química , Animales , Antibacterianos/farmacología , Escherichia coli , Ésteres , Estructura Molecular , Poríferos/química , Pirroles/química , Espectrometría de Masas en Tándem
15.
Arch Pharm (Weinheim) ; 355(4): e2100441, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35099085

RESUMEN

Microbial strains isolated from extreme and understudied environments, such as caves, are still poorly investigated for the production of bioactive secondary metabolites. Investigation of the ethyl acetate extract from the growth medium produced by the soil-derived fungus Aspergillus sp. SDC28, isolated from a Brazilian cave, yielded two anthraquinones: versicolorin C (1) and versiconol (2). The complete assignment of nuclear magnetic resonance and mass spectroscopic data of 1 and 2 was performed for the first time. Moreover, the yet unreported absolute configuration of both compounds was unambiguously established by analysis of experimental and theoretical electronic circular dichroism data. Vibrational circular dichroism was also applied to confirm the absolute stereochemistry of 2. Compounds 1 and 2 showed cytotoxic activity against human ovarian cancer cells (OVCAR3).


Asunto(s)
Cuevas , Neoplasias Ováricas , Antraquinonas/farmacología , Apoptosis , Aspergillus/química , Aspergillus/metabolismo , Brasil , Línea Celular Tumoral , Dicroismo Circular , Femenino , Humanos , Estructura Molecular , Oligodesoxirribonucleótidos , Suelo , Relación Estructura-Actividad , Tionucleótidos
16.
Dalton Trans ; 51(4): 1489-1501, 2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-34989381

RESUMEN

We have synthesized and characterized three new ruthenium(II) diphosphine complexes containing an acylthiourea ligand, with the general formula [Ru(DPEPhos)(O,S)(bipy)]PF6, where DPEPhos = bis(2-(diphenylphosphino)phenyl)ether, bipy = 2,2'-bipyridine, and O,S = N,N-dimethyl-N'-(benzoyl)thiourea (1), N,N-dimethyl-N'-(furoyl)thiourea (2), and N,N-dimethyl-N'-(thiophenyl)thiourea (3), by several physicochemical techniques. We evaluated the ruthenium complexes for their cytotoxicity against two human cancer cell lines, A549 (lung) and MDA-MB-231 (breast), and two corresponding lines of non-cancer cells, MRC-5 (lung) and MCF-10A (breast). All the complexes are cytotoxic against the cancer cell lines; the IC50 values lie in the micromolar range (0.07-0.70 µM). Ruthenium complex 1 is more selective (7 times more active) toward lung cancer cells (A549) than toward non-cancer cells (MRC-5) and is 160 times more cytotoxic than cisplatin against A549 cells. Investigations of the mechanism of action of complex 1 in A549 cells demonstrated that it inhibits colony formation and promotes cell cycle arrest in the G1 phase and apoptotic cell death. DNA binding studies revealed that complexes 1-3 interact with the biomolecule via minor grooves. These complexes also interact with human serum albumin (HSA) and have affinity for site I by hydrophobic forces. Therefore, this new class of ruthenium complexes can act as cytotoxic agents, mainly for lung cancer treatment.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Complejos de Coordinación/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos de Rutenio/farmacología , Tiourea/análogos & derivados , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Complejos de Coordinación/uso terapéutico , Femenino , Humanos , Compuestos de Rutenio/síntesis química , Compuestos de Rutenio/uso terapéutico , Tiourea/química
17.
Chem Biodivers ; 19(3): e202100757, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35092349

RESUMEN

Candida species are responsible for causing invasive candidiasis with high mortality rate and their resistance to available antifungal drugs is a major clinical challenge. Biotransformation process of the labdane diterpene ent-labd-8(17)-en-15,18-dioic acid (1) carried out with Cunninghamella elegans afforded five new derivatives (compounds 2-6). Unusual regioselective hydroxylation of the methyl group at the C-20 position of labdane-type diterpene was achieved and all compounds were subjected to cytotoxicity and antifungal evaluations. Compound 1 and its derivatives were not cytotoxic to normal (MCF-10A) and tumor (MCF-7) cell lines. Compounds 2 and 3 exhibited fungistatic activity against all tested Candida strains at lower concentrations than fluconazole. Both compounds also showed the strongest fungicidal activity against C. albicans, which is the most prevalent fungal agent involved in candidemia.


Asunto(s)
Candida , Diterpenos , Antifúngicos/farmacología , Biotransformación , Candida/metabolismo , Cunninghamella , Diterpenos/metabolismo , Diterpenos/farmacología , Fluconazol , Pruebas de Sensibilidad Microbiana
18.
Environ Sci Pollut Res Int ; 29(14): 20921-20938, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34748175

RESUMEN

The year 2020 was atypical due to the pandemic caused by the SARS-CoV-2 virus (COVID-19), providing a unique opportunity to understand changes in air quality due to the reduction in urban activity. Therefore, the aim of the present study was to perform an integrated evaluation on the influence of the effects of the 2020 pandemic on air quality in the city of Fortaleza, investigating levels of PM2.5, PM10, NO2, NO, SO2, CO, and O3, corresponding health risks, as well as the influence of meteorological variables and urban activity. In all phases analyzed, significant reductions were found in NOx, NO, NO2, and CO. A considerable reduction in PM2.5 and PM10 was found in the early phases, with an increase in the later phases. These findings are explained by the nearly 50% reduction in vehicular traffic and the consequent reduction in fossil fuel emissions, mainly in the partial lockdown and total lockdown periods, as well as reductions in commercial (stores/shops) and industrial activities. The variation in O3 was initially non-significant, followed by a considerable increase in the last three phases analyzed; this increase was influenced by changes in temperature and the incidence of sunlight. SO2 concentrations increased in the period studied, demonstrating that the vehicular fleet, local commerce, and other activities are not the predominant sources of this compound. Estimated health risks were reduced by half during the lockdown period, especially for non-smokers, followed by a drastic increase in the last three phases. The planetary boundary layer was positively correlated with O3 and PM10 and negatively correlated with NOx, NO2, and NO, indicating its influence on the distribution of pollutants in the lower atmosphere and, consequently, air quality.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Brasil/epidemiología , COVID-19/epidemiología , Ciudades , Control de Enfermedades Transmisibles , Monitoreo del Ambiente , Humanos , Pandemias , Material Particulado/análisis , SARS-CoV-2
19.
Inorg Chem ; 60(18): 14174-14189, 2021 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-34477373

RESUMEN

Ruthenium(II) complexes (Ru1-Ru5), with the general formula [Ru(N-S)(dppe)2]PF6, bearing two 1,2-bis(diphenylphosphino)ethane (dppe) ligands and a series of mercapto ligands (N-S), have been developed. The combination of these ligands in the complexes endowed hydrophobic species with high cytotoxic activity against five cancer cell lines. For the A549 (lung) and MDA-MB-231 (breast) cancer cell lines, the IC50 values of the complexes were 288- to 14-fold lower when compared to cisplatin. Furthermore, the complexes were selective for the A549 and MDA-MB-231 cancer cell lines compared to the MRC-5 nontumor cell line. The multitarget character of the complexes was investigated by using calf thymus DNA (CT DNA), human serum albumin, and human topoisomerase IB (hTopIB). The complexes potently inhibited hTopIB. In particular, complex [Ru(dmp)(dppe)2]PF6 (Ru3), bearing the 4,6-diamino-2-mercaptopyrimidine (dmp) ligand, effectively inhibited hTopIB by acting on both the cleavage and religation steps of the catalytic cycle of this enzyme. Molecular docking showed that the Ru1-Ru5 complexes have binding affinity by active sites on the hTopI and hTopI-DNA, mainly via π-alkyl and alkyl hydrophobic interactions, as well as through hydrogen bonds. Complex Ru3 displayed significant antitumor activity against murine melanoma in mouse xenograph models, but this complex did not damage DNA, as revealed by Ames and micronucleus tests.


Asunto(s)
Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , ADN-Topoisomerasas de Tipo I/metabolismo , Fosfinas/farmacología , Rutenio/farmacología , Inhibidores de Topoisomerasa I/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ligandos , Fosfinas/química , Rutenio/química , Inhibidores de Topoisomerasa I/síntesis química , Inhibidores de Topoisomerasa I/química , Células Tumorales Cultivadas
20.
Angew Chem Int Ed Engl ; 60(29): 15891-15898, 2021 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-33961724

RESUMEN

Although swarming motility and biofilms are opposed collective behaviors, both contribute to bacterial survival and host colonization. Pseudovibrio bacteria have attracted attention because they are part of the microbiome of healthy marine sponges. Two-thirds of Pseudovibrio genomes contain a member of a nonribosomal peptide synthetase-polyketide synthase gene cluster family, which is also found sporadically in Pseudomonas pathogens of insects and plants. After developing reverse genetics for Pseudovibrio, we isolated heptapeptides with an ureido linkage and related nonadepsipeptides we termed pseudovibriamides A and B, respectively. A combination of genetics and imaging mass spectrometry experiments showed heptapetides were excreted, promoting motility and reducing biofilm formation. In contrast to lipopeptides widely known to affect motility/biofilms, pseudovibriamides are not surfactants. Our results expand current knowledge on metabolites mediating bacterial collective behavior.


Asunto(s)
Péptidos/metabolismo , Poríferos/genética , Poríferos/metabolismo , Animales , Familia de Multigenes/genética , Péptido Sintasas/genética , Péptido Sintasas/metabolismo , Sintasas Poliquetidas/genética , Sintasas Poliquetidas/metabolismo , Simbiosis
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