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1.
Hum Genomics ; 17(1): 109, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38062537

RESUMO

The unique physiological and genetic characteristics of individuals influence their reactions to different dietary constituents and nutrients. This notion is the foundation of personalized nutrition. The field of nutrigenetics has witnessed significant progress in understanding the impact of genetic variants on macronutrient and micronutrient levels and the individual's responsiveness to dietary intake. These variants hold significant value in facilitating the development of personalized nutritional interventions, thereby enabling the effective translation from conventional dietary guidelines to genome-guided nutrition. Nevertheless, certain obstacles could impede the extensive implementation of individualized nutrition, which is still in its infancy, such as the polygenic nature of nutrition-related pathologies. Consequently, many disorders are susceptible to the collective influence of multiple genes and environmental interplay, wherein each gene exerts a moderate to modest effect. Furthermore, it is widely accepted that diseases emerge because of the intricate interplay between genetic predisposition and external environmental influences. In the context of this specific paradigm, the utilization of advanced "omic" technologies, including epigenomics, transcriptomics, proteomics, metabolomics, and microbiome analysis, in conjunction with comprehensive phenotyping, has the potential to unveil hitherto undisclosed hereditary elements and interactions between genes and the environment. This review aims to provide up-to-date information regarding the fundamentals of personalized nutrition, specifically emphasizing the complex triangulation interplay among microbiota, dietary metabolites, and genes. Furthermore, it highlights the intestinal microbiota's unique makeup, its influence on nutrigenomics, and the tailoring of dietary suggestions. Finally, this article provides an overview of genotyping versus microbiomics, focusing on investigating the potential applications of this knowledge in the context of tailored dietary plans that aim to improve human well-being and overall health.


Assuntos
Metabolômica , Nutrigenômica , Humanos , Estado Nutricional , Predisposição Genética para Doença , Estilo de Vida Saudável
2.
J Med Genet ; 59(8): 801-809, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34400559

RESUMO

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Here, we investigate the genetic architecture of MG via a genome-wide association study (GWAS) of the largest MG data set analysed to date. METHODS: We performed GWAS meta-analysis integrating three different data sets (total of 1401 cases and 3508 controls). We carried out human leucocyte antigen (HLA) fine-mapping, gene-based and tissue enrichment analyses and investigated genetic correlation with 13 other autoimmune disorders as well as pleiotropy across MG and correlated disorders. RESULTS: We confirmed the previously reported MG association with TNFRSF11A (rs4369774; p=1.09×10-13, OR=1.4). Furthermore, gene-based analysis revealed AGRN as a novel MG susceptibility gene. HLA fine-mapping pointed to two independent MG loci: HLA-DRB1 and HLA-B. MG onset-specific analysis reveals differences in the genetic architecture of early-onset MG (EOMG) versus late-onset MG (LOMG). Furthermore, we find MG to be genetically correlated with type 1 diabetes (T1D), rheumatoid arthritis (RA), late-onset vitiligo and autoimmune thyroid disease (ATD). Cross-disorder meta-analysis reveals multiple risk loci that appear pleiotropic across MG and correlated disorders. DISCUSSION: Our gene-based analysis identifies AGRN as a novel MG susceptibility gene, implicating for the first time a locus encoding a protein (agrin) that is directly relevant to NMJ activation. Mutations in AGRN have been found to underlie congenital myasthenic syndrome. Our results are also consistent with previous studies highlighting the role of HLA and TNFRSF11A in MG aetiology and the different risk genes in EOMG versus LOMG. Finally, we uncover the genetic correlation of MG with T1D, RA, ATD and late-onset vitiligo, pointing to shared underlying genetic mechanisms.


Assuntos
Artrite Reumatoide , Diabetes Mellitus Tipo 1 , Miastenia Gravis , Vitiligo , Idade de Início , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Miastenia Gravis/genética
3.
Harm Reduct J ; 20(1): 147, 2023 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-37838658

RESUMO

BACKGROUND: Flavored e-cigarettes remain a controversial topic with regulators planning or already implementing restrictions worldwide. In this study, we examined patterns of flavor use in e-cigarettes among a convenience sample of US adult vapers. METHODS: Participants aged ≥ 18 years who reported ever using an e-cigarette were included in the study (N = 69,233) and responded to an online questionnaire. Their smoking status was recorded as well as patterns of flavor use at e-cigarette use initiation, at the time of the survey and at the time of smoking cessation (for participants who used to smoke and were using e-cigarettes at the time of quitting). RESULTS: The most popular flavors at e-cigarette use initiation were fruit (82.8%), followed by dessert/pastry/bakery (68.6%) and candy/chocolate/sweet (52.2%). Slightly higher prevalence of using fruit and dessert/pastry/bakery flavors was observed in those who never smoked compared to those who were currently and formerly smoking. Tobacco flavors were used by 20.8% of the participants and was by far the least prevalent among participants who never smoked. Similar patterns were observed with participants' choices at the time of the survey, but tobacco flavor use was substantially reduced (7.7%). Only 2.1% reported tobacco as the single most often used flavor. The most prevalent flavor at the time of quitting smoking was again fruit (83.3%), followed by dessert/pastry/bakery (68.0%) and candy/chocolate/sweet (44.5%). These flavors were considered the most helpful for quitting smoking. Tobacco flavor use at the time of smoking cessation was reported by 15.0%, while 9.3% considered it helpful for quitting smoking. CONCLUSION: Non-tobacco flavors were popular among the US adult vapers who participated in the study, and were popular choices at the time of quitting smoking for those who formerly smoked. Tobacco flavor use prevalence was low and was further reduced over time. Regulators should consider the flavor choice of adult consumers, especially those who quit smoking, when preparing legislation on flavored e-cigarettes.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Vaping , Adulto , Humanos , Estados Unidos/epidemiologia , Fumantes , Estudos Transversais , Vaping/epidemiologia , Aromatizantes
4.
Molecules ; 25(20)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086510

RESUMO

The ubiquitin pathway required for most proteins' targeted degradation involves three classes of enzymes: E1-activating enzyme, E2-conjugating enzyme, and E3-ligases. The human Ark2C is the single known E3 ligase that adopts an alternative, Ub-dependent mechanism for the activation of Ub transfer in the pathway. Its RING domain binds both E2-Ub and free Ub with high affinity, resulting in a catalytic active UbR-RING-E2-UbD complex formation. We examined potential changes in the conformational plasticity of the Ark2C RING domain and its ligands in their complexed form within the ubiquitin pathway through molecular dynamics (MD). Three molecular mechanics force fields compared to previous NMR relaxation studies of RING domain of Arkadia were used for effective and accurate assessment of MDs. Our results suggest the Ark2C Ub-RING docking site has a substantial impact on maintaining the conformational rigidity of E2-E3 assembly, necessary for the E3's catalytic activity. In the UbR-RING-E2-UbD catalytic complex, the UbR molecule was found to have greater mobility than the other Ub, bound to E2. Furthermore, network-based bioinformatics helped us identify E3 RING ligase candidates which potentially exhibit similar structural modules as Ark2C, along with predicted substrates targeted by the Ub-binding RING Ark2C. Our findings could trigger a further exploration of related unrevealed functions of various other E3 RING ligases.


Assuntos
Conformação Proteica , Mapas de Interação de Proteínas/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina/genética , Cristalografia por Raios X , Humanos , Simulação de Dinâmica Molecular , Ligação Proteica/genética , Enzimas de Conjugação de Ubiquitina/química , Enzimas de Conjugação de Ubiquitina/genética , Ubiquitinação/genética
5.
Harm Reduct J ; 16(1): 48, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345235

RESUMO

INTRODUCTION: A recent study raised concerns about e-cigarette liquids toxicity by reporting the presence of 14 flavouring chemicals with toxicity classification. However, the relevant toxicity classification was not estimated according to the measured concentrations. The purpose of this study was to calculate the toxicity classification for different health hazards for all the flavouring chemicals at the maximum concentrations reported. METHODS: The analysis was based on the European Union Classification Labelling and Packaging regulation. The concentration of each flavouring chemical was compared with the minimum concentration needed to classify it as toxic. Additionally, toxicity classification was examined for a theoretical e-cigarette liquid containing all flavouring chemicals at the maximum concentrations reported. RESULTS: There was at least one toxicity classification for all the flavouring chemicals, with the most prevalent classifications related to skin, oral, eye and respiratory toxicities. One chemical (methyl cyclopentenolone) was found at a maximum concentration 150.7% higher than that needed to be classified as toxic. For the rest, the maximum reported concentrations were 71.6 to > 99.9% lower than toxicity concentrations. A liquid containing all flavouring compounds at the maximum concentrations would be classified as toxic for one category only due to the presence of methyl cyclopentenolone; a liquid without methyl cyclopentenolone would have 66.7 to > 99.9% lower concentrations of flavourings than those needed to be classified as toxic. CONCLUSIONS: The vast majority of flavouring compounds in e-cigarette liquids as reported in a recent study were present at levels far lower than needed to classify them as toxic. Since exceptions exist, regulatory monitoring of liquid composition is warranted.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/classificação , Aromatizantes/classificação , Aromatizantes/toxicidade , Substâncias Perigosas/classificação , Substâncias Perigosas/toxicidade , Relação Dose-Resposta a Droga , União Europeia , Olho/efeitos dos fármacos , Humanos , Boca/efeitos dos fármacos , Sistema Respiratório/efeitos dos fármacos , Pele/efeitos dos fármacos
6.
Electromagn Biol Med ; 38(3): 218-229, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31079506

RESUMO

Although rehabilitation practice for most patients consists of a combined use of thermotherapy that is produced from diathermy devices resulting faster and deeper heating to the patient, major concerns about occupational exposure to electromagnetic radiation for the operators must be considered. In most occasions, physiotherapists have involved multi-hour treatment sessions to different patients, resulting overuse of the diathermy device. Recently, our team along with other groups have raised serious concerns about the occupational safety aspects related to microwave diathermy (MWD) use. Driven by these recent reports, in this work, we tried to investigate the in vitro effects of a physiotherapist routine MWD device regarding its potential inflammatory biological effects that could be evoked in human cultured monocytes. Our results show that MWD does not alter the integrity of the cell membrane and, consequently, the viability of monocytes as assessed by Trypan blue and MTT measurements. Then again, members of the MAPK family (p38 and ERK1/2) were activated upon MWD exposure at 5-30 min, eventually leading to a time-dependent considerable increase in TNF-α production, a key pro-inflammatory mediator. Our results are indicative of a stress-activated phenomenon of monocytes upon MWD radiation, which could trigger potential hazardous cellular outcomes due to thermal and/or non-thermal bystander effects. Our results deserve further investigation, planned by our team in due course, to delineate the clinical correlations of these findings.


Assuntos
Diatermia , Micro-Ondas , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monócitos/metabolismo , Monócitos/efeitos da radiação , Fator de Necrose Tumoral alfa/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos da radiação , Ativação Enzimática/efeitos da radiação , Humanos , Espaço Intracelular/metabolismo , Espaço Intracelular/efeitos da radiação , Monócitos/citologia
7.
Bioinformatics ; 31(4): 581-6, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25332376

RESUMO

MOTIVATION: An autoimmune disorder occurs when the immune system mistakenly attacks and destroys its own healthy body tissues. The initiation of a geoepidemiological database, for recording autoimmune incidents with a focus to clinical manifestations, demographic parameters and geographic background is crucial to detect correlations. RESULTS: The dAUTObase collects an ever increasing number of publications-currently counting 435-on autoimmune diseases' frequencies in various populations and ethnic groups. The respective data have been hosted by a web application developed for the task. It uses three data visualization tools: the PivotViewer, the Disease Treemap and the Disease World Map, to assist the effective data querying. AVAILABILITY AND IMPLEMENTATION: The dAUTObase 2.0 version (www.biodata.gr/dautobase) needs no registration for querying, but data entry and modification is reserved for registered users (curators-administrators). CONTACT: kpoulas@upatras.gr or tzimas@cti.gr.


Assuntos
Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Biologia Computacional/métodos , Bases de Dados Genéticas , Etnicidade/genética , Genoma Humano , Software , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/genética , Feminino , Genética Populacional/métodos , Saúde Global , Humanos , Masculino , Síndrome
8.
Clin Neuropathol ; 34(6): 359-63, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26365462

RESUMO

AIM: Muscle specific kinase (MuSK) antibody-positive myasthenia gravis(MG) patients might present with clinical and electrophysiological signs of muscle atrophy. In this study, we investigated the potential contribution of mitochondrial dysfunction to muscle atrophy induced by MuSK immunity. METHODS: Mitochondrial enzyme expression was investigated in muscle samples of MuSK-immunized, acetylcholine receptor (AChR)-immunized, and complete Freund's adjuvant (CFA)-immunized C57BL/6 (B6) mice using histochemical methods. Mitochondrial enzyme activity was also investigated in MuSK- and CFA-immunized mice. RESULTS: Histochemical analysis showed normal muscle fiber activity on succinate dehydrogenase (SDH) and cytochrome oxidase (COX) stains in all immunization groups. However, MuSK-immunized mice had more ragged-red fibers on modified Gomori-trichrome (MGT) stain and more pronounced type 1 muscle fiber atrophy. MuSK-immunized mice also showed reduced citrate synthase, SDH, and NADH-cytochrome c-reductase activity. DISCUSSION: Our results suggest that MuSK-immunity might induce muscle atrophy through mitochondrial dysfunction.


Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Mitocôndrias/enzimologia , Doenças Musculares/enzimologia , Miastenia Gravis/enzimologia , Fosfotransferases/imunologia , Succinato Desidrogenase/metabolismo , Animais , Autoanticorpos/imunologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
9.
Toxics ; 11(11)2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37999555

RESUMO

Environmental pollution is a growing threat to natural ecosystems and one of the world's most pressing concerns. The increasing worldwide use of pharmaceuticals has elevated their status as significant emerging contaminants. Pharmaceuticals enter aquatic environments through multiple pathways related to anthropogenic activity. Their high consumption, insufficient waste treatment, and the incapacity of organisms to completely metabolize them contribute to their accumulation in aquatic environments, posing a threat to all life forms. Various analytical methods have been used to quantify pharmaceuticals. Biotechnology advancements based on next-generation sequencing (NGS) techniques, like eDNA metabarcoding, have enabled the development of new methods for assessing and monitoring the ecotoxicological effects of pharmaceuticals. eDNA metabarcoding is a valuable biomonitoring tool for pharmaceutical pollution because it (a) provides an efficient method to assess and predict pollution status, (b) identifies pollution sources, (c) tracks changes in pharmaceutical pollution levels over time, (d) assesses the ecological impact of pharmaceutical pollution, (e) helps prioritize cleanup and mitigation efforts, and (f) offers insights into the diversity and composition of microbial and other bioindicator communities. This review highlights the issue of aquatic pharmaceutical pollution while emphasizing the importance of using modern NGS-based biomonitoring actions to assess its environmental effects more consistently and effectively.

10.
Front Immunol ; 14: 1147573, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37809097

RESUMO

Introduction: Autoimmune disorders (ADs) are a group of about 80 disorders that occur when self-attacking autoantibodies are produced due to failure in the self-tolerance mechanisms. ADs are polygenic disorders and associations with genes both in the human leukocyte antigen (HLA) region and outside of it have been described. Previous studies have shown that they are highly comorbid with shared genetic risk factors, while epidemiological studies revealed associations between various lifestyle and health-related phenotypes and ADs. Methods: Here, for the first time, we performed a comparative polygenic risk score (PRS) - Phenome Wide Association Study (PheWAS) for 11 different ADs (Juvenile Idiopathic Arthritis, Primary Sclerosing Cholangitis, Celiac Disease, Multiple Sclerosis, Rheumatoid Arthritis, Psoriasis, Myasthenia Gravis, Type 1 Diabetes, Systemic Lupus Erythematosus, Vitiligo Late Onset, Vitiligo Early Onset) and 3,254 phenotypes available in the UK Biobank that include a wide range of socio-demographic, lifestyle and health-related outcomes. Additionally, we investigated the genetic relationships of the studied ADs, calculating their genetic correlation and conducting cross-disorder GWAS meta-analyses for the observed AD clusters. Results: In total, we identified 508 phenotypes significantly associated with at least one AD PRS. 272 phenotypes were significantly associated after excluding variants in the HLA region from the PRS estimation. Through genetic correlation and genetic factor analyses, we identified four genetic factors that run across studied ADs. Cross-trait meta-analyses within each factor revealed pleiotropic genome-wide significant loci. Discussion: Overall, our study confirms the association of different factors with genetic susceptibility for ADs and reveals novel observations that need to be further explored.


Assuntos
Doenças Autoimunes , Diabetes Mellitus Tipo 1 , Vitiligo , Humanos , Doenças Autoimunes/genética , Diabetes Mellitus Tipo 1/genética , Antígenos HLA , Fenótipo , Polimorfismo de Nucleotídeo Único
11.
Antioxidants (Basel) ; 11(11)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36421460

RESUMO

BACKGROUND: Calorie restriction is known to enhance Nrf2 signaling and longevity in adult mice, partially by reducing reactive oxygen species, but calorie restriction during pregnancy leads to intrauterine growth retardation. The latter is associated with fetal reprogramming leading to increased incidence of obesity, metabolic syndrome and diabetes in adult life. Transcription factor Nrf2 is a central regulator of the antioxidant response and its crosstalk with metabolic pathways is emerging. We hypothesized that the Nrf2 pathway is induced in embryos during calorie restriction in pregnant mothers. METHODS: From gestational day 10 up to day 16, 50% of the necessary mouse diet was provided to Nrf2 heterozygous pregnant females with fathers being of the same genotype. Embryos were harvested at the end of gestational day 16 and fetal liver was used for qRT-PCR and assessment of oxidative stress (OS). RESULTS: Intrauterine calorie restriction led to upregulation of mRNA expression of antioxidant genes (Nqo1, Gsta1, Gsta4) and of genes related to integrated stress response (Chac1, Ddit3) in WT embryos. The expression of a key gluconeogenic (G6pase) and two lipogenic genes (Acacb, Fasn) was repressed in calorie-restricted embryos. In Nrf2 knockout embryos, the induction of Nqo1 and Gsta1 genes was abrogated while that of Gsta4 was preserved, indicating an at least partially Nrf2-dependent induction of antioxidant genes after in utero calorie restriction. Measures of OS showed no difference (superoxide radical and malondialdehyde) or a small decrease (thiobarbituric reactive substances) in calorie-restricted WT embryos. CONCLUSIONS: Calorie restriction during pregnancy elicits the transcriptional induction of cytoprotective/antioxidant genes in the fetal liver, which is at least partially Nrf2-dependent, with a physiological significance that warrants further investigation.

12.
Hum Genomics ; 4(5): 361-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20650823

RESUMO

National and ethnic mutation databases (NEMDBs) are emerging online repositories, recording extensive information about the described genetic heterogeneity of an ethnic group or population. These resources facilitate the provision of genetic services and provide a comprehensive list of genomic variations among different populations. As such, they enhance awareness of the various genetic disorders. Here, we describe the features of the ETHNOS software, a simple but versatile tool based on a flat-file database that is specifically designed for the development and curation of NEMDBs. ETHNOS is a freely available software which runs more than half of the NEMDBs currently available. Given the emerging need for NEMDB in genetic testing services and the fact that ETHNOS is the only off-the-shelf software available for NEMDB development and curation, its adoption in subsequent NEMDB development would contribute towards data content uniformity, unlike the diverse contents and quality of the available gene (locus)-specific databases. Finally, we allude to the potential applications of NEMDBs, not only as worldwide central allele frequency repositories, but also, and most importantly, as data warehouses of individual-level genomic data, hence allowing for a comprehensive ethnicity-specific documentation of genomic variation.


Assuntos
Biologia Computacional/métodos , Bases de Dados Genéticas , Software , Etnicidade/genética , Genótipo , Humanos , Israel , Anotação de Sequência Molecular , Mutação/genética , Fenótipo
13.
Food Chem Toxicol ; 149: 112009, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33503469

RESUMO

SARS-CoV-2 is the coronavirus that originated in Wuhan in December 2019 and has spread globally. Studies have shown that smokers are less likely to be diagnosed with or be hospitalized for COVID-19 but, once hospitalized, have higher odds for an adverse outcome. We have previously presented the potential interaction between SARS-CoV-2 Spike glycoprotein and nicotinic acetylcholine receptors (nAChRs), due to a "toxin-like" epitope on the Spike glycoprotein, with homology to a sequence of a snake venom toxin. This epitope coincides with the well-described cryptic epitope for the human anti-SARS-CoV antibody CR3022. In this study, we present the molecular complexes of both SARS-CoV and SARS-CoV-2 Spike glycoproteins, at their open or closed conformations, with the model of the human α7 nAChR. We found that all studied protein complexes' interface involves a large part of the "toxin-like" sequences of SARS-CoV and SARS-CoV-2 Spike glycoproteins and toxin binding site of human α7 nAChR. Our findings provide further support to the hypothesis about the protective role of nicotine and other cholinergic agonists. The potential therapeutic role of CR3022 and other similar monoclonal antibodies with increased affinity for SARS-CoV-2 Spike glycoprotein against the clinical effects originating from the dysregulated cholinergic pathway should be further explored.


Assuntos
COVID-19/virologia , Epitopos , Nicotina/farmacologia , SARS-CoV-2/química , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/química , Glicoproteína da Espícula de Coronavírus/química , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Sequência de Aminoácidos , Anticorpos Monoclonais/química , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/química , Anticorpos Antivirais/uso terapêutico , Sítios de Ligação de Anticorpos , COVID-19/metabolismo , COVID-19/prevenção & controle , Humanos , Modelos Moleculares , Agonistas Nicotínicos/química , Agonistas Nicotínicos/uso terapêutico , Sistema Colinérgico não Neuronal , Pandemias , Fatores de Proteção , Conformação Proteica , Homologia de Sequência , Transdução de Sinais , Fumantes , Fumar , Venenos de Serpentes/química
14.
Toxicol Rep ; 8: 73-83, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33425684

RESUMO

SARS-CoV-2 infection was announced as a pandemic in March 2020. Since then, several scientists have focused on the low prevalence of smokers among hospitalized COVID-19 patients. These findings led to our hypothesis that the Nicotinic Cholinergic System (NCS) plays a crucial role in the manifestation of COVID-19 and its severe symptoms. Molecular modeling revealed that the SARS-CoV-2 Spike glycoprotein might bind to nicotinic acetylcholine receptors (nAChRs) through a cryptic epitope homologous to snake toxins, substrates well documented and known for their affinity to the nAChRs. This binding model could provide logical explanations for the acute inflammatory disorder in patients with COVID-19, which may be linked to severe dysregulation of NCS. In this study, we present a series of complexes with cholinergic agonists that can potentially prevent SARS-CoV-2 Spike glycoprotein from binding to nAChRs, avoiding dysregulation of the NCS and moderating the symptoms and clinical manifestations of COVID-19. If our hypothesis is verified by in vitro and in vivo studies, repurposing agents currently approved for smoking cessation and neurological conditions could provide the scientific community with a therapeutic option in severe COVID-19.

15.
Eur J Immunol ; 39(3): 730-40, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19197942

RESUMO

The immune response to pathogen is regulated by a combination of specific PRR, which are involved in pathogen recognition. Pseudomonas aeruginosa, a bacterium that causes life-threatening disease in immuno-compromised host, is recognized by distinct members of the TLR family. We have previously shown that viable P. aeruginosa bacteria are recognized by human monocytes mainly through TLR2. Using ligand-specific blocking antibodies, we herein show that the mannose receptor (MR), a phagocytic receptor for unopsonized P. aeruginosa bacteria, contributes equally to TLR2 in proinflammatory cytokine production by human monocytes in response to P. aeruginosa infection. Synergy of both receptors totally controls the immune response. Viable P. aeruginosa bacteria activate NF-kappaB and MAPK pathways and enhance TLR2-mediated signaling in MR-transfected human embryonic kidney 293 cells. Moreover, MR follows the same kinetics and colocalizes with TLR2 in the endosome during in vivo infection of human macrophages with P. aeruginosa. The studies provide the first demonstration of a significant role for MR, synergistic with TLR2, in activating a proinflammatory response to P. aeruginosa infection.


Assuntos
Lectinas Tipo C/imunologia , Lectinas de Ligação a Manose/imunologia , Monócitos/imunologia , Infecções por Pseudomonas/imunologia , Receptores de Superfície Celular/imunologia , Receptor 2 Toll-Like/imunologia , Linhagem Celular , Células Cultivadas , Humanos , Interleucina-1beta/biossíntese , Interleucina-1beta/imunologia , Interleucina-6/biossíntese , Interleucina-6/imunologia , Lectinas Tipo C/metabolismo , Receptor de Manose , Lectinas de Ligação a Manose/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/imunologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Monócitos/metabolismo , Monócitos/microbiologia , Fagocitose/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/imunologia , Receptores de Superfície Celular/metabolismo , Receptor 2 Toll-Like/metabolismo , Transfecção , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologia , Quinase Induzida por NF-kappaB
16.
Cont Lens Anterior Eye ; 43(3): 277-284, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32111452

RESUMO

Addiction to cigarette smoking has high prevalence rates recorded worldwide. Smoking has been linked to several life-threatening systemic conditions such as cancer, heart attack and stroke, in addition to a range of ocular pathologies. In recent years, electronic cigarettes (EC) have emerged as alternatives to smoking. ECs are nicotine delivery devices which produce an aerosol by heating, rather than combusting, a liquid which contains nicotine, flavours and preservatives. This review focuses on the association of traditional and new forms of smoking with dry eye disease, contact lens wear and four other common ocular diseases: cataract, age-related macular degeneration, glaucoma and Graves' ophthalmopathy. It is concluded that smoking and vaping appear as a risk factor for the aforementioned ocular conditions. An evidence-based, clear link between cigarette smoking, or EC vaping and ocular problems is yet to be discovered.


Assuntos
Síndromes do Olho Seco/etiologia , Sistemas Eletrônicos de Liberação de Nicotina , Fumar/efeitos adversos , Síndromes do Olho Seco/epidemiologia , Saúde Global , Humanos , Prevalência , Fatores de Risco , Fumar/epidemiologia
18.
Biosensors (Basel) ; 9(3)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31492004

RESUMO

Chronic pressure ulcers are hard-to-heal wounds that decrease the patient's quality of life. Wireless Micro Current Stimulation (WMCS) is an innovative, non-invasive, similar to electrode-based electrostimulation (ES) technology, that generates and transfers ions that are negatively-charged to the injured tissue, using accessible air gases as a transfer medium. WMCS is capable of generating similar tissue potentials, as electrode-based ES, for injured tissue. Here, through immunohistochemistry, we intended to characterize the induced tissue healing biological mechanisms that occur during WMCS therapy. Two single cases of bedridden due to serious stroke white men with chronic non-healing pressure ulcers have been treated with WMCS technology. WMCS suppresses inflammatory responses by decreasing the aggregation of granulocytes, followed by stimulating myofibroblastic activity and a new formation of collagen fibers, as depicted by immunohistochemistry. As a result, WMCS provides a special adjunct or stand-alone therapy choice for chronic and non-healing injuries, similar to electrode-based ES, but with added (i.e., contactless) benefits towards its establishment as a routine clinical wound healing regime.


Assuntos
Imuno-Histoquímica/métodos , Cicatrização/fisiologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade
19.
Toxics ; 7(3)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480224

RESUMO

Cigarette smoke is a complex mixture of chemical compounds which are emitted during the processes of tobacco combustion. Electronic cigarettes (e-cigs) are expected to produce less harmful compounds due to the absence of tobacco leaf combustion. However, potential risks of the passive exposure to the aerosol exhaled by e-cig users have been raised in the last decade. In this study, the aerosols with diameter less than 1 µm (PM1) produced by vaping of various e-cig liquids were compared to those generated by smoking conventional cigarettes in real time. The mass and number concentration along with the number size distribution were measured in a closed room of 35 m3 volume. Our results showed that aerosols emitted from e-cig liquids had a different profile compared to those from conventional cigarettes. Although e-cigs initially produced higher particle mass and number concentrations, their emissions had much shorter lifetime of approximately 10-20 s, in comparison with the conventional and hand-rolling cigarette particulate emissions which had a dissipation time of approximately 1.4 h in a 35 m3 room. E-cigs emitted aerosols which volatilized rapidly, as they probably consisted almost only of propylene glycol and/or vegetable glycerin.

20.
J Neuroimmunol ; 200(1-2): 133-41, 2008 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-18603305

RESUMO

Myasthenia gravis (MG) is an autoimmune disease usually caused by autoantibodies against the muscle nicotinic acetylcholine receptor (nAChR), found at the neuromuscular junction. Current treatments for the disease, including plasmapheresis, are not antigen-specific, and thus often cause severe side effects. The development and implementation of new therapeutic approaches for the disease attain particular importance, since the number of diagnosed myasthenic patients has increased considerably. In order to develop an antigen-specific approach for the selective depletion of anti-nAChR autoantibodies from MG patients' sera, we have expressed the extracellular domains (ECDs) of all human muscle nAChR subunits in E. coli. These recombinant proteins were immobilized on CNBr-Sepharose and used in immunoadsorption assays with MG sera. We showed that, despite being purified from E. coli under denaturing conditions, these recombinant ECDs could be successfully used as immunoadsorbents with a comparable efficiency to the corresponding ECDs produced in water-soluble form in the yeast Pichia pastoris. The high yield of the ECDs, the stability of the constructed ECD resins and the high selectivity for anti-nAChR antibodies increase the therapeutic potential of the system.


Assuntos
Autoanticorpos/imunologia , Remoção de Componentes Sanguíneos/métodos , Escherichia coli/imunologia , Miastenia Gravis/sangue , Receptores Nicotínicos/imunologia , Humanos , Miastenia Gravis/imunologia , Miastenia Gravis/terapia , Estrutura Terciária de Proteína , Receptores Nicotínicos/genética , Receptores Nicotínicos/uso terapêutico , Fatores de Tempo
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