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1.
Nanomaterials (Basel) ; 11(8)2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34443815

RESUMEN

BACKGROUND: Pathogenic intracellular mycobacteria are challenging to treat because of the waxy and complex cell wall characterizing the genus. Niosomes are vesicles with biomimetic cell membrane composition, which allow them to efficiently bind to the eukaryotic cells and deliver their cargo into the cytoplasm. The objective of this study was to develop a new platform based on niosomes loaded with antimicrobial agents to target intracellular mycobacteria. Nanoniosomes were fabricated and loaded with antibiotics and lignin-silver nanoparticles. The efficacy of these nanoniosomes was tested against the intracellular pathogen Mycobacterium abscessus used as a model of infection of human-derived macrophages (THP-1). The cytotoxicity and the immunological response of the agents were tested on THP-1 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the secretion of pro- and anti-inflammatory cytokines, respectively. RESULTS: M. abscessus was susceptible to the nanoniosomes in infected THP-1 macrophages, suggesting that the nanoniosomes were internalized due to their fusion to the macrophage cellular membrane. Moreover, nanoniosomes showed no upregulation of pro-inflammatory cytokines when exposed to THP-1 macrophages. CONCLUSIONS: Nanoniosomes improved drug efficacy while decreasing toxicity and should be considered for further testing in the treatment of intracellular pathogenic mycobacteria or as a new platform for precise intracellular delivery of drugs.

2.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-34445366

RESUMEN

Lung cancer is the leading cause of cancer-related deaths in North America and other developed countries. One of the reasons lung cancer is at the top of the list is that it is often not diagnosed until the cancer is at an advanced stage. Thus, the earliest diagnosis of lung cancer is crucial, especially in screening high-risk populations, such as smokers, exposure to fumes, oil fields, toxic occupational places, etc. Based on the current knowledge, it looks that there is an urgent need to identify novel biomarkers. The current diagnosis of lung cancer includes different types of imaging complemented with pathological assessment of biopsies, but these techniques can still not detect early lung cancer developments. In this review, we described the advantages and disadvantages of current methods used in diagnosing lung cancer, and we provide an analysis of the potential use of body fluids as carriers of biomarkers as predictors of cancer development and progression.


Asunto(s)
Neoplasias Pulmonares/diagnóstico , Enfermedades Profesionales/diagnóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Biopsia , Diagnóstico por Imagen , Progresión de la Enfermedad , Detección Precoz del Cáncer , Humanos , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Enfermedades Profesionales/etiología , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiología
3.
J Appl Microbiol ; 2021 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-34134177

RESUMEN

INTRODUCTION: Nanoparticles (NPs) have been widely studied as an alternative to antibiotic use due to their antimicrobial properties at lower concentrations. Enterococcus faecalis is a facultative Gram-positive microorganism inhabiting the gastrointestinal tract of humans and animals. It can also be present in other environments such as the oral cavity, water, sewage, soil and food. AIMS: We evaluated whether E. faecalis could develop resistance to silver NPs (AgNPs) after exposure to sublethal concentrations of the NPs. METHODS AND RESULTS: Proteomic analyses revealed that different pathways were activated during the acquired resistance under sublethal concentrations, and selected genes were validated by qPCR. CONCLUSIONS: The results of this study showed that E. faecalis is capable of generating resistance to AgNPs. SIGNIFICANCE AND IMPACT OF THE STUDY: To avoid the generation of resistance against AgNPs, future use of these NPs should be combined with other NPs prepared with different metals to prevent the dissemination of resistant strains.

4.
Future Sci OA ; 7(6): FSO704, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-34046206

RESUMEN

Aim: To explore the bioactivities of commercial fragrances. Materials & methods: The antimicrobial activity of 25 commercial fragrances was assessed with pathogenic bacteria and fungi in vapor phase. Inflammatory response was evaluated by the measurement of cytokines. Results: Several fragrances were able to kill the microorganisms. Moreover, preparations of binary mixtures of the most active fragrances showed a synergistic effect. Regarding the inflammatory response, none of the tested fragrances showed a pro-inflammatory response, but two fragrances upregulated the secretion of IL-10 from macrophages. Conclusion: The antimicrobial activities of fragrances represent a new approach to control airborne pathogens.

5.
ACS Appl Mater Interfaces ; 13(19): 22098-22109, 2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-33945683

RESUMEN

The emergence of bacteria resistant to antibiotics and the resulting infections are increasingly becoming a public health issue. Multidrug-resistant (MDR) bacteria are responsible for infections leading to increased morbidity and mortality in hospitals, prolonged time of hospitalization, and additional burden to financial costs. Therefore, there is an urgent need for novel antibacterial agents that will both treat MDR infections and outsmart the bacterial evolutionary mechanisms, preventing further resistance development. In this study, a green synthesis employing nontoxic lignin as both reducing and capping agents was adopted to formulate stable and biocompatible silver-lignin nanoparticles (NPs) exhibiting antibacterial activity. The resulting silver-lignin NPs were approximately 20 nm in diameter and did not agglomerate after one year of storage at 4 °C. They were able to inhibit the growth of a panel of MDR clinical isolates, including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii, at concentrations that did not affect the viability of a monocyte-derived THP-1 human cell line. Furthermore, the exposure of silver-lignin NPs to the THP-1 cells led to a significant increase in the secretion of the anti-inflammatory cytokine IL-10, demonstrating the potential of these particles to act as an antimicrobial and anti-inflammatory agent simultaneously. P. aeruginosa genes linked with efflux, heavy metal resistance, capsular biosynthesis, and quorum sensing were investigated for changes in gene expression upon sublethal exposure to the silver-lignin NPs. Genes encoding for membrane proteins with an efflux function were upregulated. However, all other genes were membrane proteins that did not efflux metals and were downregulated.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Lignina/química , Nanopartículas del Metal , Plata/química , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Humanos , Inflamación/prevención & control , Pruebas de Sensibilidad Microbiana , Células THP-1
6.
Int J Pharm ; 596: 120299, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33524525

RESUMEN

Due to the increasing inability of antibiotics to treat multidrug-resistant (MDR) bacteria, metal and metal oxide nanoparticles have been gaining interest as antimicrobial agents. Among those, silver nanoparticles have been used extensively as broad-spectrum antimicrobial agents. Here, we describe a newly-developed, 10-min (120 °C at 5 bar pressure) microwave-assisted synthesis of silver nanoparticles made from the wood biopolymer lignin as a reducing and capping agent. The resulting lignin-capped silver nanoparticles (AgLNPs) had an average particle diameter of 13.4 ±â€¯2.8 nm. Antimicrobial susceptibility assays against a variety of MDR clinical Gram-positive and Gram-negative pathogens revealed a minimal inhibitory concentration (MIC) of AgLNPs ≤5 µg/mL. AgLNPs (10 µg/mL) showed ≤20% cytotoxicity towards monocytic THP-1 cells and were well tolerated when administered subcutaneously in mice at high concentrations (5 mg at a concentration of 100 mg/mL) with no obvious toxicity. AgLNPs showed efficacy in an in vivo infection (abscess) mouse model against MDR Pseudomonas aeruginosa LESB58 and methicillin-resistant Staphylococcus aureus USA300. A significant decrease in abscess sizes was observed for both strains as well as a reduction in bacterial loads of P. aeruginosa after three days. This demonstrates that microwave-assisted synthesis provides an optimized strategy for the production of AgLNPs while maintaining antimicrobial activity in vitro and in vivo.


Asunto(s)
Antiinfecciosos , Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina , Animales , Antibacterianos/farmacología , Lignina , Ratones , Pruebas de Sensibilidad Microbiana , Microondas , Pseudomonas aeruginosa , Plata
7.
Microorganisms ; 9(1)2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33451069

RESUMEN

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, was first reported in December 2019 in Wuhan, Hubei province, China. This virus has led to 61.8 million cases worldwide being reported as of December 1st, 2020. Currently, there are no definite approved therapies endorsed by the World Health Organization for COVID-19, focusing only on supportive care. Treatment centers around symptom management, including oxygen therapy or invasive mechanical ventilation. Immunotherapy has the potential to play a role in the treatment of SARS-CoV-2. Monoclonal antibodies (mAbs), in particular, is a relatively new approach in the world of infectious diseases and has the benefit of overcoming challenges with serum therapy and intravenous immunoglobulins preparations. Here, we reviewed the articles published in PubMed with the purpose of summarizing the currently available evidence for the use of neutralizing antibodies as a potential treatment for coronaviruses. Studies reporting in vivo results were summarized and analyzed. Despite promising data from some studies, none of them progressed to clinical trials. It is expected that neutralizing antibodies might offer an alternative for COVID-19 treatment. Thus, there is a need for randomized trials to understand the potential use of this treatment.

8.
Foods ; 10(2)2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33494180

RESUMEN

Wheat grains are exposed to several plagues after harvesting and during storage. These plagues include bacteria, fungi, and insects with detrimental outcomes to their quality and heavy losses to the farmers. Fungi are of special interest because of their ability to produce mycotoxins with health concerns. Once grains are harvested, synthetic fungicides, which are sprayed before long-term storage, normally control fungi; however, these synthetic products represent a health concern because of their toxicities. Previously, we reported the antifungal activity of the essential oils extracted from Porophyllum linaria, Agastache mexicana, and Buddleja perfoliata against fungal strains isolated from stored wheat. In this study, we sprayed wheat grains with the same essential oils to measure their persistence interval and to prepare baked products to assess potential changes in their physical properties. The persistence interval of the essential oils in grains indicated that it takes between 63 and 134 days to eliminate 90% of the original compounds. This extended time of the compounds in the grains together with a lack of physical properties modifications of the flour and baked products (post-treatment) suggest that the presence of oils in the grains is potentially safe to use. The solid data denote the technological feasibility of the treatment and the possible management of residues through adequate safety intervals.

10.
Microorganisms ; 8(12)2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-33371478

RESUMEN

Mycobacterium avium subspecies paratuberculosis (MAP) has long been suspected to be involved in the etiology of Crohn's disease (CD). An obligate intracellular pathogen, MAP persists and influences host macrophages. The primary goals of this study were to test new rapid culture methods for MAP in human subjects and to assess the degree of viable culturable MAP bacteremia in CD patients compared to controls. A secondary goal was to compare the efficacy of three culture methods plus a phage assay and four antibody assays performed in separate laboratories, to detect MAP from the parallel samples. Culture and serological MAP testing was performed blind on whole blood samples obtained from 201 subjects including 61 CD patients (two of the patients with CD had concurrent ulcerative colitis (UC)) and 140 non-CD controls (14 patients in this group had UC only). Viable MAP bacteremia was detected in a significant number of study subjects across all groups. This included Pozzato culture (124/201 or 62% of all subjects, 35/61 or 57% of CD patients), Phage assay (113/201 or 56% of all subjects, 28/61 or 46% of CD patients), TiKa culture (64/201 or 32% of all subjects, 22/61 or 36% of CD patients) and MGIT culture (36/201 or 18% of all subjects, 15/61 or 25% of CD patients). A link between MAP detection and CD was observed with MGIT culture and one of the antibody methods (Hsp65) confirming previous studies. Other detection methods showed no association between any of the groups tested. Nine subjects with a positive Phage assay (4/9) or MAP culture (5/9) were again positive with the Phage assay one year later. This study highlights viable MAP bacteremia is widespread in the study population including CD patients, those with other autoimmune conditions and asymptomatic healthy subjects.

11.
Clin Microbiol Infect ; 26(10): 1436-1446, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32791241

RESUMEN

BACKGROUND: There is currently no treatment known to alter the course of coronavirus disease 2019 (COVID-19). Convalescent plasma has been used to treat a number of infections during pandemics, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome coronavirus (MERS-CoV) and now severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). OBJECTIVES: To summarize the existing literature and registered clinical trials on the efficacy and safety of convalescent plasma for treating coronaviruses, and discuss issues of feasibility, and donor and patient selection. SOURCES: A review of articles published in PubMed was performed on 13 July 2020 to summarize the currently available evidence in human studies for convalescent plasma as a treatment for coronaviruses. The World Health Organization International Clinical Trials Registry and clinicaltrials.gov were searched to summarize the currently registered randomized clinical trials for convalescent plasma in COVID-19. CONTENT: There were sixteen COVID-19, four MERS and five SARS reports describing convalescent plasma use in humans. There were two randomized control trials, both of which were for COVID-19 and were terminated early. Most COVID-19 reports described a potential benefit of convalescent plasma on clinical outcomes in severe or critically ill patients with few immediate adverse events. However, there were a number of limitations, including the concurrent use of antivirals, steroids and other treatments, small sample sizes, lack of randomization or control groups, and short follow-up time. Data from SARS and COVID-19 suggest that earlier administration probably yields better outcomes. The ideal candidates for recipients and donors are not known. Still, experience with previous coronaviruses tells us that antibodies in convalescent patients are probably short-lived. Patients who had more severe disease and who are earlier in their course of recovery may be more likely to have adequate titres. Finally, a number of practical challenges were identified. IMPLICATIONS: There is currently no effective treatment for COVID-19, and preliminary trials for convalescent plasma suggest that there may be some benefits. However, research to date is at high risk of bias, and randomized control trials are desperately needed to determine the efficacy and safety of this therapeutic option.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Síndrome Respiratorio Agudo Grave/epidemiología , Síndrome Respiratorio Agudo Grave/terapia , Antivirales/uso terapéutico , Betacoronavirus/patogenicidad , COVID-19 , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Humanos , Inmunización Pasiva/métodos , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Seguridad del Paciente , Neumonía Viral/diagnóstico , Neumonía Viral/mortalidad , Virus del SRAS/patogenicidad , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave/diagnóstico , Síndrome Respiratorio Agudo Grave/mortalidad , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del Tratamiento
12.
Microorganisms ; 8(7)2020 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-32635236

RESUMEN

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP), a member of the mycobacteriaceae family, causes Johne's disease in ruminants, which resembles Crohn's disease (CD) in humans. MAP was proposed to be one of the causes of human CD, but the evidence remains elusive. Macrophages were reported to be the only cell where MAP proliferates in ruminants and humans and is likely the major producer of TNFα-associated inflammation. However, whether human dendritic cells (DCs), another major antigen-presenting cell (APC), have the ability to harbor MAP and disseminate infection, remains unknown. METHODS: Human monocyte-derived dendritic cells (moDCs) were infected with MAP and phagocytosis and intracellular survival were quantified by immunofluorescence (IF) and colony counts, respectively. MoDC cytokine expression was measured via ELISA and their activation state was measured via flow cytometry. RESULTS: We showed that MAP can infect and replicate in human moDCs as means to evade the immune system for successful infection, through inhibition of the phago-lysosome fusion via the secretion of protein tyrosine phosphatase PtpA. This mechanism initially led to a state of tolerance in moDCs and then subsequently caused a pro-inflammatory response as infection persisted, characterized by the upregulation of IL-6 and TNFα, and downregulation of IL-10. Moreover, we showed that moDCs have the ability to phagocytose up to 18% of MAP, when exposed at a multiplicity of infection of 1:1. CONCLUSION: Infection and subsequent proliferation of MAP within moDCs could provide a unique means for the dissemination of MAP to lymphoid tissue, while altering immune responses to facilitate the persistence of infection of host tissues in CD.

13.
Microorganisms ; 8(8)2020 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-32707942

RESUMEN

The virus SARS-CoV-2, the etiological agent of COVID-19, is responsible for more than 400,000 deaths worldwide as of 10 June 2020. As a result of its recent appearance (December 2019), an efficacious treatment is not yet available. Although considered a lung infection since its emergence, COVID-19 is now causing multiple organ failure, requiring a continuous adjustment in the procedures. In this review, we summarize the current literature surrounding unproven therapies for COVID-19. Analyses of the clinical trials were grouped as chemotherapy, serotherapy, anticoagulant, and the use of human recombinant soluble ACE2 therapies. We conclude that, while no agent has hit the threshold for quality of evidence to demonstrate efficacy and safety, preliminary data show potential benefits. Moreover, there is a possibility for harm with these unproven therapies, and the decision to treat should be based on a comprehensive risk-benefit analysis.

14.
Nat Prod Res ; : 1-8, 2020 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-32375531

RESUMEN

The new labdane [(3R*,4aR*,7S*,10aS*,10bR*)-3-ethenyl-3,4a,7,10a-tetramethyl-dodecahydro-1H-naphtho-[2,1-b]-pyran-7-yl]-methylbenzoate together with other 7 labdanes were isolated from the aerial parts of Buddleja marrubiifolia. Compound structures were elucidated by spectroscopic methods. Some compounds showed moderate to weak antimicrobial activity towards a panel of bacterial and fungal pathogens. In addition, trans-biformene (2) and ribenol acetate (8) showed to be highly cytotoxic with LC50 < 1 µg/mL, the other compounds showed moderate cytotoxic effect with a LC50 range of 6.008-15.26 µg/mL. For all isolated compounds, no inflammatory response was observed.

15.
J Biomed Mater Res B Appl Biomater ; 108(2): 333-342, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31041849

RESUMEN

Biofilms are matrices synthesized by bacteria containing polysaccharides, DNA, and proteins. The development of biofilms in infectious processes can induce a chronic inflammatory response that may progress to the destruction of tissues. The treatment of biofilms is difficult because they serve as a bacterial mechanism of defense and high doses of antibiotics are necessary to treat these infections with limited positive results. It has been demonstrated that photothermal therapy using gold nanorods (AuNRs) is an attractive treatment because of its anti-biofilm activity. The purpose of this work was to generate a novel chitosan-based hydrogel embedded with AuNRs to evaluate its anti-biofilm activity. AuNRs were synthesized by the seed-mediated growth method and mixed with the chitosan-based hydrogel. Hydrogels were characterized and tested against two bacterial strains by irradiating the produced biofilm in the presence of the nanoformulation with a laser adjusted at the near infrared spectrum. In addition, the safety of the nanoformulation was assessed with normal human gingival fibroblasts. Results showed that a significant bacterial killing was measured when biofilms were exposed to an increase of 10°C for a short time of 2 min. Moreover, no cytotoxicity was measured when normal gingival fibroblasts were exposed to the nanoformulation using the bactericidal conditions. The development of the reported formulation can be used as a direct application to treat periodontal diseases or biofilm-produced bacteria that colonize the oral cavity.


Asunto(s)
Antibacterianos/química , Biopelículas/efectos de los fármacos , Quitosano/química , Oro/química , Hidrogeles/química , Nanotubos/química , Fármacos Fotosensibilizantes/química , Antibacterianos/farmacología , Supervivencia Celular/efectos de los fármacos , Desinfección , Composición de Medicamentos , Enterococcus faecalis/efectos de los fármacos , Fibroblastos/citología , Encía/citología , Oro/farmacología , Calor , Humanos , Rayos Infrarrojos , Rayos Láser , Viabilidad Microbiana/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Terapia Fototérmica , Streptococcus oralis/efectos de los fármacos
16.
J Inflamm Res ; 12: 301-308, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31819587

RESUMEN

Purpose: Rheumatoid arthritis (RA) can result from complex interactions between the affected person's genetic background and environment. Viral and bacterial infections may play a pathogenetic role in RA through different mechanisms of action. We aimed to evaluate the presence of antibodies (Abs) directed against two proteins of Mycobacterium avium subsp. paratuberculosis (MAP) in sera of RA subjects, which are crucial for the survival of the pathogen within macrophages. Moreover, we analyzed the correlation of immune response to both proteins with the following homologous peptides: BOLF1305-320, MAP_402718-32 and IRF5424-434 to understand how the synergic role of Epstein-Barr virus (EBV) and MAP infection in genetically predisposed subjects may lead to a possible deregulation of interferon regulatory factor 5 (IRF5). Materials and methods: The presence of Abs against protein tyrosine phosphatase A (PtpA) and protein kinase G (PknG) in sera from Sardinian RA patients (n=84) and healthy volunteers (HCs, n=79) was tested by indirect ELISA. Results: RA sera showed a remarkably high frequency of reactivity against PtpA in comparison to HCs (48.8% vs 7.6%; p<0.001) and lower but statistically significant responses towards PknG (27.4% vs 10.1%; p=0.0054). We found a significant linear correlation between the number of swollen joints and the concentrations of antibodies against PtpA (p=0.018). Furthermore, a significant bivariate correlation between PtpA and MAP MAP_402718-32 peptide has been found, suggesting that MAP infection may induce a secondary immune response through cross-reaction with IRF5 (R2=0.5). Conclusion: PtpA and PknG are strongly recognized in RA which supports the hypothesis that MAP infection may be involved in the pathogenesis of RA.

17.
Nanomedicine ; 22: 102093, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31521833

RESUMEN

Plasmonic photothermal therapy (PPTT) has been used as an alternative to chemotherapy for the elimination of resistant microorganisms; however, its in situ evaluation has not been well studied. In the present study, we assessed the antimicrobial activity of a chitosan-based hydrogel embedded with gold nanorods (Ch/AuNRs) using a low power infrared diode laser. The antibacterial activity was measured in both Gram-positive and -negative strains, including clinical isolates of multidrug-resistant pathogens. The cytotoxic effect, cellular proliferation, and the expression of the pro-inflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines were quantified in a murine model of macrophages. Results showed a potent antimicrobial activity of the Ch/AuNRs with MICs ≤4 µg/mL, very low cytotoxicity with cell viability above 80%, and the macrophage proliferation was not affected for a period of 48 h. These results suggest that our Ch/AuNR-embedded hydrogel could be an option to locally control chronic nosocomial infections using PPTT.


Asunto(s)
Antiinfecciosos/farmacología , Oro/farmacología , Hidrogeles/farmacología , Hipertermia Inducida , Nanotubos/química , Fototerapia , Animales , Antifúngicos/farmacología , Bromodesoxiuridina/metabolismo , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quitosano/química , Inflamación/patología , Ratones , Pruebas de Sensibilidad Microbiana , Nanotubos/ultraestructura , Células RAW 264.7
18.
Future Sci OA ; 5(7): FSO400, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31428447

RESUMEN

Aim: Spermidine/spermine N1-acetyltransferase (SSAT-1) regulates cell growth, proliferation and death. Amantadine is converted by SSAT-1 to acetylamantadine (AA). In our earlier studies, although SSAT-1 was activated in patients with cancer, a number of ostensibly healthy adult volunteers had higher than expected AA concentration. This study was therefore undertaken to examine the outlier group. Materials & methods: A follow up of urine analysis for AA by liquid chromatography-tandem mass spectrometry as well as clinical assessments and additional blood analyses were conducted. Results: In some of the outlier controls, higher than expected AA concentration was linked to increased serum carcinoembryonic antigen. Clinical and radiographic assessments revealed underlying abnormalities in other cases that could represent premalignant conditions. Hematology tests revealed elevations in white blood cells and platelets, which are markers of inflammation. Conclusion: High urine concentration of AA could be used as a simple and useful test for screening of cancer in high-risk populations.

19.
Proc Natl Acad Sci U S A ; 116(33): 16326-16331, 2019 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-31366629

RESUMEN

Phase separation drives numerous cellular processes, ranging from the formation of membrane-less organelles to the cooperative assembly of signaling proteins. Features such as multivalency and intrinsic disorder that enable condensate formation are found not only in cytosolic and nuclear proteins, but also in membrane-associated proteins. The ABC transporter Rv1747, which is important for Mycobacterium tuberculosis (Mtb) growth in infected hosts, has a cytoplasmic regulatory module consisting of 2 phosphothreonine-binding Forkhead-associated domains joined by an intrinsically disordered linker with multiple phospho-acceptor threonines. Here we demonstrate that the regulatory modules of Rv1747 and its homolog in Mycobacterium smegmatis form liquid-like condensates as a function of concentration and phosphorylation. The serine/threonine kinases and sole phosphatase of Mtb tune phosphorylation-enhanced phase separation and differentially colocalize with the resulting condensates. The Rv1747 regulatory module also phase-separates on supported lipid bilayers and forms dynamic foci when expressed heterologously in live yeast and M. smegmatis cells. Consistent with these observations, single-molecule localization microscopy reveals that the endogenous Mtb transporter forms higher-order clusters within the Mycobacterium membrane. Collectively, these data suggest a key role for phase separation in the function of these mycobacterial ABC transporters and their regulation via intracellular signaling.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Proteínas de la Membrana/genética , Mycobacterium tuberculosis/genética , Tuberculosis/genética , Transportadoras de Casetes de Unión a ATP/química , Citosol/metabolismo , Regulación Bacteriana de la Expresión Génica/genética , Humanos , Membrana Dobles de Lípidos/metabolismo , Proteínas de la Membrana/ultraestructura , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/patogenicidad , Mycobacterium tuberculosis/patogenicidad , Mycobacterium tuberculosis/ultraestructura , Proteínas Nucleares/genética , Fosforilación/genética , Transducción de Señal/genética , Imagen Individual de Molécula , Tuberculosis/microbiología
20.
Biomed Res Int ; 2019: 1639726, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31205934

RESUMEN

Essential oils (EOs) are natural products composed of a mixture of volatile and aromatic compounds extracted from different parts of plants that have shown antimicrobial activities against pathogens. In this study, EOs extracted from Pimenta dioica (Myrtaceae) and Rosmarinus officinalis (Lamiaceae) were assessed for their antimicrobial activities using a panel of pathogenic Gram-positive, Gram-negative, and fungal strains. The antimicrobial activity was measured by the minimal inhibitory concentration required for the growth inhibition of the microorganisms. The cytotoxicity of the EOs was tested ex vivo using the model of human-derived macrophage THP-1 cells. In addition, an inflammatory response was evaluated using the anti-inflammatory cytokine IL-10 and the proinflammatory cytokines IL-6 and TNF-α. Results showed that both EOs had antimicrobial activity and different pathogens were exposed to concentrations ranging between 600 and 2000 µg/mL. In addition, the EOs showed no inflammatory activity when exposed to human macrophages, but a potent anti-inflammatory activity was measured when the oil from Rosmarinus officinalis was exposed to macrophages. This study demonstrates that the use of EOs is an effective alternative for pathogenic bacterial and fungal control, alone or in combination with antibiotic therapy. Moreover, the oil extracted from Rosmarinus officinalis could be used as potent anti-inflammatory agent.


Asunto(s)
Antiinfecciosos/farmacología , Antiinflamatorios/farmacología , Citotoxinas/farmacología , Género Pimenta/química , Aceites Volátiles/farmacología , Rosmarinus/química , Antiinfecciosos/química , Antiinflamatorios/química , Bacterias/crecimiento & desarrollo , Citotoxinas/química , Hongos/crecimiento & desarrollo , Humanos , Aceites Volátiles/química , Células THP-1
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