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Vagus nerve regulates viral infection and inflammation via the alpha 7 nicotinic acetylcholine receptor (α7 nAChR); however, the role of α7 nAChR in ZIKA virus (ZIKV) infection, which can cause severe neurological diseases such as microcephaly and Guillain-Barré syndrome, remains unknown. Here, we first examined the role of α7 nAChR in ZIKV infection in vitro. A broad effect of α7 nAChR activation was identified in limiting ZIKV infection in multiple cell lines. Combined with transcriptomics analysis, we further demonstrated that α7 nAChR activation promoted autophagy and ferroptosis pathways to limit cellular ZIKV viral loads. Additionally, activation of α7 nAChR prevented ZIKV-induced p62 nucleus accumulation, which mediated an enhanced autophagy pathway. By regulating proteasome complex and an E3 ligase NEDD4, activation of α7 nAChR resulted in increased amount of cellular p62, which further enhanced the ferroptosis pathway to reduce ZIKV infection. Moreover, utilizing in vivo neonatal mouse models, we showed that α7 nAChR is essential in controlling the disease severity of ZIKV infection. Taken together, our findings identify an α7 nAChR-mediated effect that critically contributes to limiting ZIKV infection, and α7 nAChR activation offers a novel strategy for combating ZIKV infection and its complications.
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Autofagia , Ferroptosis , Infección por el Virus Zika , Virus Zika , Receptor Nicotínico de Acetilcolina alfa 7 , Infección por el Virus Zika/virología , Infección por el Virus Zika/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/genética , Animales , Virus Zika/fisiología , Ratones , Humanos , Modelos Animales de Enfermedad , Línea Celular , Carga ViralRESUMEN
BACKGROUND: Reactive Red (RR) 141 dye is widely used in various industrial applications, but its environmental impact remains a growing concern. In this study, the phytotoxic and genotoxic effects of RR 141 dye on mung bean seedlings (Vigna radiata (L.) Wilczek) were investigated, serving as a model for potential harm to plant systems. METHODS AND RESULTS: Short-term (14 days) and long-term (60 days) experiments in paddy soil pot culture exposed mung bean seedlings to RR 141 dye. The dye delayed germination and hindered growth, significantly reducing germination percentage and seedling vigor index (SVI) at concentrations of 50 and 100 ml/L. In short-term exposure, plumule and radical lengths dose-dependently decreased, while long-term exposure affected plant length and grain weight, leaving pod-related parameters unaffected. To evaluate genotoxicity, high annealing temperature-random amplified polymorphic DNA (HAT-RAPD) analysis was employed with five RAPD primers having 58-75% GC content. It detected polymorphic band patterns, generating 116 bands (433 to 2857 bp) in plant leaves exposed to the dye. Polymorphisms indicated the appearance/disappearance of DNA bands in both concentrations, with decreased genomic template stability (GTS) values suggesting DNA damage and mutation. CONCLUSION: These findings demonstrate that RR 141 dye has a significant impact on genomic template stability (GTS) and exhibits phytotoxic and genotoxic responses in mung bean seedlings. This research underscores the potential of RR 141 dye to act as a harmful agent within plant model systems, highlighting the need for further assessment of its environmental implications.
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Alcaloides , Vigna , Vigna/genética , Plantones , Técnica del ADN Polimorfo Amplificado Aleatorio , Daño del ADN , ADNRESUMEN
INTRODUCTION: Contrast nephropathy (CN) is characterized by oxidative stress, vasoconstriction, tubular toxicity, and hypoxia of the renal medulla. We aimed to test the therapeutic effects of an α7 nicotinic acetylcholine receptor (nAChR) agonist, GTS-21, in an experimental CN model. METHODS: Male Sprague-Dawley rats (n = 40) were divided into 4 groups: saline-treated control, GTS-21-treated control, contrast, and GTS-21-treated contrast groups. Starting on the 1st day, GTS-21 (4 mg/kg, intraperitoneally) or saline was administered twice a day for 3 days. CN was induced on the second day by intravenous injection of indomethacin (10 mg/kg),
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Medios de Contraste , Enfermedades Renales , Ratas Sprague-Dawley , Receptor Nicotínico de Acetilcolina alfa 7 , Animales , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Masculino , Ratas , Medios de Contraste/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Modelos Animales de Enfermedad , Estrés Oxidativo/efectos de los fármacos , Agonistas Nicotínicos/farmacología , Agonistas Nicotínicos/uso terapéutico , Quinuclidinas , Compuestos Bicíclicos Heterocíclicos con PuentesRESUMEN
Two main objectives were pursued to assess the reliability of Thuja orientalis essential oils (TOEO). The first objective was to extract TOEO, analyze them by GC-MS, and determine their inâ vitro genotoxicity against selected plants using the RAPD-PCR method. The second objective was to evaluate the in-silico toxicity of TOEO. The binding sites and energies of each content was calculated against B-DNA. In-silico analyses were performed using a simulation program, AutoDock Vina, and Toxicity Estimation Software Tools. 3-carene, cedrol, and 2-pinene were identified as the predominant components. In vitro studies showed that the TOEO had a more significant impact on reducing genomic stability in wheat compared to the amaranth. The lowest stability was determined as 39.78 % in wheat and 53.58 % in amaranth. Cedrol (-5,7â kcal/mol) and selinene (-5,6â kcal/mol) exhibited the highest binding affinity. The toxicity test indicated that components other than cyclohexene may have toxic effects, none of them were predicted to be mutagenic, and LD50 (mol/kg) values could vary between 1.33 and 1.55.
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Aceites Volátiles , Sesquiterpenos Policíclicos , Thuja , Aceites Volátiles/química , Thuja/química , Técnica del ADN Polimorfo Amplificado Aleatorio , Reproducibilidad de los Resultados , Simulación del Acoplamiento MolecularRESUMEN
BACKGROUND: Lavender (genus Lavandula, family Lamiaceae) is an aromatic plant widely grown as an ornamental plant. The chemical composition of lavender is characterized by monoterpenoids, sesquiterpenoids, and other compounds, which are primarily synthesized and stored in epidermal secretory structures called glandular trichomes (GTs). Volatile organic compounds (VOCs) are responsible for the aroma characteristics of plant oil that drive consumer preference. Aroma is usually regarded as a characteristic trait for the classification of aromatic plants. Interestingly, VOCs are synthesized and stored in GTs. Lamiaceae species such as purple perilla, peppermint, basil, thyme, and oregano usually possess two types of GTs: peltate glandular trichomes (PGTs) and capitate glandular trichomes (CGTs). But the development process of PGTs in lavender has been reported in only a few studies to date. RESULTS: In this study, we identified and quantified the VOCs in four lavender cultivars by headspace-solid phase micro extraction-gas chromatography mass spectrometry (HS-SPME-GC-MS). A total of 66 VOCs were identified in these four cultivars, the most prominent of which were linalyl acetate and linalool, and flowers were the main site of accumulation of these VOCs. Here, we examined the developmental process of PGTs, including the formation of their base, body, and apex. The apex cells contained secretory cavities, which produced VOCs. Based on the reference genome sequence of the lavender cultivar 'Jingxun 2', several R2R3-MYB subfamily genes related to GT formation were identified. These results will guide the engineering of GTs and molecular breeding of lavender for improving the VOC content. CONCLUSIONS: In this study, we identified the VOCs in four lavender cultivars. We analyzed the formation of GTs, and compared the number and diameter size of PGTs among four lavender cultivars. Additionally, we identified four candidate genes belonging to the R2R3-MYB family.
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Lavandula , Aceites Volátiles , Terpenos , Lavandula/genética , Aceites Volátiles/análisis , Tricomas/química , Aceites de Plantas/químicaRESUMEN
We discuss models for the activation and desensitization of α7 nicotinic acetylcholine receptors (nAChRs) and the effects of efficacious type II positive allosteric modulators (PAMs) that destabilize α7 desensitized states. Type II PAMs such as PNU-120596 can be used to distinguish inactive compounds from silent agonists, compounds that produce little or no channel activation but stabilize the non-conducting conformations associated with desensitization. We discuss the effects of α7 nAChRs in cells of the immune system and their roles in modulating inflammation and pain through what has come to be known as the cholinergic anti-inflammatory system (CAS). Cells controlling CAS do not generate ion channel currents but rather respond to α7 drugs by modulating intracellular signaling pathways analogous to the effects of metabotropic receptors. Metabotropic signaling by α7 receptors appears to be mediated by receptors in nonconducting conformations and can be accomplished by silent agonists. We discuss electrophysiological structure-activity relationships for α7 silent agonists and their use in cell-based and in vivo assays for CAS regulation. We discuss the strongly desensitizing partial agonist GTS-21 and its effectiveness in modulation of CAS. We also review the properties of the silent agonist NS6740, which is remarkably effective at maintaining α7 receptors in PAM-sensitive desensitized states. Most silent agonists bind to sites overlapping those for orthosteric agonists, but some appear to bind to allosteric sites. Finally, we discuss α9* nAChRs and their potential role in CAS, and ligands that will be useful in defining and distinguishing the specific roles of α7 and α9 in CAS.
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Receptores Nicotínicos , Receptor Nicotínico de Acetilcolina alfa 7 , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Regulación Alostérica , Receptores Nicotínicos/metabolismo , Relación Estructura-Actividad , AntiinflamatoriosRESUMEN
Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD4+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.
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It was previously established that the original dipeptide mimetic of the 4th loop of NT-3, hexamethylenediamide bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) (GTS-301), has a pronounced neuroprotective effect in vitro at concentrations of 10-5-10-12 Ð. In the present study, experiments on the streptozotocin-induced diabetes model in C57Bl/6 mice showed that GTS-301, when administered intraperitoneally for 32 days at doses of 0.1 and 0.5 mg/kg, has antidiabetic activity manifested in a reduction of hyperglycemia and polydipsia and in an increase in animal survival. The results obtained confirm the concept of the similarity of neurochemical mechanisms underlying the regulation of functions of neurons and ß-cells.
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Diabetes Mellitus Experimental , Fármacos Neuroprotectores , Peptidomiméticos , Ratones , Animales , Dipéptidos/farmacología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Neuronas , Fármacos Neuroprotectores/farmacología , Peptidomiméticos/farmacologíaRESUMEN
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common malignant tumor that seriously affects human health. Previous studies have indicated that abnormal levels of glycosylation promote progression and poor prognosis of lung cancer. Thus, the present study aimed to explore the prognostic signature related to glycosyltransferases (GTs) for LUAD. METHODS: The gene expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and GTs were obtained from the GlycomeDB database. Differentially expressed GTs-related genes (DGTs) were identified using edge package and Venn diagram. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ingenuity pathway analysis (IPA) methods were used to investigate the biological processes of DGTs. Subsequently, Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct a prognostic model for LUAD. Kaplan-Meier (K-M) analysis was adopted to explore the overall survival (OS) of LUAD patients. The accuracy and specificity of the prognostic model were evaluated by receiver operating characteristic analysis (ROC). In addition, single-sample gene set enrichment analysis (ssGSEA) algorithm was used to analyze the infiltrating immune cells in the tumor environment. RESULTS: A total of 48 DGTs were mainly enriched in the processes of glycosylation, glycoprotein biosynthetic process, glycosphingolipid biosynthesis-lacto and neolacto series, and cell-mediated immune response. Furthermore, B3GNT3, MFNG, GYLTL1B, ALG3, and GALNT13 were screened as prognostic genes to construct a risk model for LUAD, and the LUAD patients were divided into high- and low-risk groups. K-M curve suggested that patients with a high-risk score had shorter OS than those with a low-risk score. The ROC analysis demonstrated that the risk model efficiently diagnoses LUAD. Additionally, the proportion of infiltrating aDCs (p < 0.05) and Tgds (p < 0.01) was higher in the high-risk group than in the low-risk group. Spearman's correlation analysis manifested that the prognostic genes (MFNG and ALG3) were significantly correlated with infiltrating immune cells. CONCLUSION: In summary, this study established a novel GTs-related risk model for the prognosis of LUAD patients, providing new therapeutic targets for LUAD. However, the biological role of glycosylation-related genes in LUAD needs to be explored further.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Glicosilación , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Factores de Riesgo , Algoritmos , ManosiltransferasasRESUMEN
BACKGROUND AND AIMS: Cholinergic output, which could modulate innate immune responses through stimulation of α7 nicotinic acetylcholine receptor (α7nAChR), might be a target to minimize tissue damage in autoimmune disease. GTS-21, a selective α7nAChR agonist, has previously demonstrated to inhibit synovium inflammation in rheumatoid arthritis. In this study, we investigated the effect of GTS-21 on dextran sulfate sodium (DSS)-induced colitis model and its potential mechanism. METHODS: Male BABL/c mice (n = 32) were randomly divided into four groups: normal control group, DSS-induced colitis group, GTS-21 treatment with or without α7nAChR antagonist α-BGT treatment group. Disease activity index (DAI), histological activity index (HAI) and colonic macroscopic damage were evaluated. Fluorescein isothiocyanate (FITC)-dextran assay was applied to measure intestinal permeability. The expressions of tight junction (TJ) proteins and NF-κB associated proteins were detected by Western blot. RESULTS: GTS-21 could decrease DAI scores, HAI scores, intestinal permeability and reduce the intestinal bacterial translocation in DSS-induced colitis group, whereas α7nAChR antagonist α-BGT could impair this protective influence. The expressions of TJ proteins were increased with administration of GTS-21 both in vivo and in vitro. Furthermore, GTS-21 also inhibited the NF-ÒB activation in intestinal epithelial cells and colitis model, while α-BGT reversed the inhibitory effect. CONCLUSION: The α7nAChR agonist GTS-21 attenuated DSS-induced colitis through increasing expressions of TJ proteins in colon tissues and improved intestinal barrier function, which might be due to modulating NF-ÒB activation in intestinal epithelial cells.
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Colitis , Receptor Nicotínico de Acetilcolina alfa 7 , Animales , Compuestos de Bencilideno/farmacología , Compuestos de Bencilideno/uso terapéutico , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colon , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Piridinas , Proteínas de Uniones Estrechas , Receptor Nicotínico de Acetilcolina alfa 7/agonistasRESUMEN
Neuroinflammation is crucial in the progression of neurodegenerative diseases. Thus, controlling neuroinflammation has been proposed as an important therapeutic strategy for neurodegenerative disease. In the present study, we examined the anti-inflammatory and neuroprotective effects of GTS-21, a selective α7 nicotinic acetylcholine receptor (α7 nAChR) agonist, in neuroinflammation and Parkinson's disease (PD) mouse models. GTS-21 inhibited the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and primary microglia. Further research revealed that GTS-21 has anti-inflammatory properties by inhibiting PI3K/Akt, NF-κB, and upregulating AMPK, Nrf2, CREB, and PPARγ signals. The effects of GTS-21 on these pro-/anti-inflammatory signaling molecules were reversed by treatment with an α7 nAChR antagonist, suggesting that the anti-inflammatory effects of GTS-21 are mediated through α7 nAChR activation. The anti-inflammatory and neuroprotective properties of GTS-21 were then confirmed in LPS-induced systemic inflammation and MPTP-induced PD model mice. In LPS-injected mouse brains, GTS-21 reduced microglial activation and production of proinflammatory markers. Furthermore, in the brains of MPTP-injected mice, GTS-21 restored locomotor activity and dopaminergic neuronal cell death while inhibiting microglial activation and pro-inflammatory gene expression. These findings suggest that GTS-21 has therapeutic potential in neuroinflammatory and neurodegenerative diseases such as PD.
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Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Enfermedad de Parkinson , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Compuestos de Bencilideno , Modelos Animales de Enfermedad , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , FN-kappa B/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neuroinflamatorias , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Agonistas Nicotínicos/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Piridinas , Receptor Nicotínico de Acetilcolina alfa 7/metabolismoRESUMEN
The dimeric dipeptide mimetic hexamethylenediamide bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) (GTS-301) was created on the basis of the structure of the exposed region of the neurotrophin-3 4th loop. The new compound, as well as the full-length neurotrophin, activated the TrkC and TrkB receptors. GTS-301 showed neuroprotective activity in experiments on HT-22 mouse hippocampal cells under conditions of oxidative stress and glutamate toxicity at concentrations of 10-12 and 10-8 M, respectively, and antidepressant-like activity in the forced swimming test on mice with 7-day intraperitoneal administration in doses of 10-40 mg/kg.
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Dipéptidos , Receptor trkB , Animales , Antidepresivos/química , Antidepresivos/farmacología , Materiales Biomiméticos , Dipéptidos/química , Dipéptidos/farmacología , Hipocampo , Ratones , Factores de Crecimiento NerviosoRESUMEN
Glycosyltransferases (GTs) catalyse the reaction of glyco-conjugation of various biomolecules by transferring the saccharide moieties from an activated nucleotide sugar to nucleophilic glycosyl acceptor. In insects, GTs show diverse temporal and site-specific expression patterns and thus play significant roles in forming the complex biomolecular structures that are necessary for insect survival, growth and development. Several insects exhibit GT-mediated detoxification as a key defence strategy against plant allelochemicals and xenobiotic compounds, as well as a mechanism for pesticide cross-resistance. Also, these enzymes act as crucial effectors and modulators in various developmental processes of insects such as eye development, UV shielding, cuticle formation, epithelial development and other specialized functions. Furthermore, many of the known insect GTs have been shown to play a fundamental role in other physiological processes like body pigmentation, cuticular tanning, chemosensation and stress response. This review provides a detailed overview of the multifaceted functionality of insect GTs and summarizes numerous case studies associated with it.
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Glicosiltransferasas , Insectos/enzimología , Insectos/crecimiento & desarrollo , Animales , Inactivación Metabólica , Insectos/metabolismoRESUMEN
Polymerase chain reaction (PCR) technology has become a standard technique for the detection of genetically modified organisms (GMOs). However, this method requires a PCR amplification process which is both expensive and time-consuming. Herein, we propose electric field-induced release and measurement (EFIRM) technology as an alternative method for GMO screening. The specificity and sensitivity of the EFIRM assay were proven to be comparable to those of the real-time PCR method for detecting genetically modified soybeans. After all the parameters had been evaluated, the actual evaluation of soybean samples from soybean cargoes was performed. An actual EFIRM screening was performed on 157 soybean cargo samples, which had 102 transgenic soybean samples containing the GTS-40-3-2 gene, through a blind trial at the Dalian port of China. Our results showed that 101 transgenic soybean samples were correctly detected, with only one false-negative case, and 55 non-transgenic soybean samples were detected as negative; this demonstrates that the EFIRM assay is an effective, accurate, simple, and economical novel method for detecting transgenic products, which may have a positive impact on the development of rapid on-site GMO monitoring platforms.
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Glycine max/genética , Plantas Modificadas Genéticamente/genética , Técnicas Biosensibles , ADN de Plantas/genética , Alimentos Modificados Genéticamente , TransgenesRESUMEN
The ubiquiotous nuclear protein HMGB1 is extracellularly released by dying cells or activated innate immunity cells to promote inflammation. Extracellular HMGB1 plays a prominent role in the pathogenesis of acute lung injury of infectious as well as sterile origin including hyperoxia. Excessive amounts of systemic HMGB1 and HMGB1-partner molecule complexes can be retained in the pulmonary circulation indicated by a substantial reduction of HMGB1 plasma levels in arterial versus venous blood. The cholinergic antiinflammatory mechanism ameliorates pulmonary inflammation by inhibiting HMGB1 release and HMGB1 receptor expression. This comprehension was recently reinforced by results reported in Molecular Medicine by Sitapara and coworkers demonstrating that administration of an α7 nicotinic acetylcholine receptor agonist attenuated hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation. Activating the cholinergic antiinflammatory path might be considered to alleviate severe COVID-19 with or without concurrent oxygen-induced lung injury.
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Lesión Pulmonar Aguda/prevención & control , Infecciones por Coronavirus/prevención & control , Proteína HMGB1/antagonistas & inhibidores , Neuroinmunomodulación/efectos de los fármacos , Agonistas Nicotínicos/uso terapéutico , Pandemias/prevención & control , Neumonía Viral/prevención & control , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/patología , Animales , Betacoronavirus/inmunología , COVID-19 , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Humanos , Neumonía Viral/inmunología , Neumonía Viral/patología , Neumonía Viral/virología , SARS-CoV-2RESUMEN
During the harvest period, tobacco workers are exposed to nicotine and it is known that absorption of the alkaloid via the leaves causes green tobacco sickness (GST). We investigated if GST and its symptoms are associated with DNA damage and alterations of the redox status. DNA damage was measured in lymphocytes of tobacco workers and controls (n = 40/group) in single cell gel electrophoresis assays. Exposure to nicotine was determined by plasma cotinine measurements, alterations of the redox status by quantification of the total antioxidant capacity (TEAC) and of thiobarbituric acid reactive substances (TBARS). The symptoms of GTS included nausea, abdominal cramps, headache, vomiting and dizziness, and 50% of the workers had more than one symptom. Cotinine levels were enhanced in the workers (111 ng/mL); furthermore, the extent of DNA damage was ca. 3-fold higher than in the controls. This effect was more pronounced in participants with GST compared to healthy nicotine exposed workers and increased in individuals with specific symptoms (range 22-36%). TBARS levels did not differ between workers and unexposed controls, while TEAC values were even increased (by 14.3%). Contact with nicotine present in tobacco leaves causes GTS and leads to damage of the DNA; this effect is more pronounced in workers with GTS symptoms and is associated with alterations of the redox status. Damage of the genetic material which was found in the workers may lead to adverse long-term effects that are caused by genomic instability such as cancer and accelerated ageing.
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Enfermedades de los Trabajadores Agrícolas/inducido químicamente , Daño del ADN , Agricultores , Nicotiana/crecimiento & desarrollo , Nicotina/toxicidad , Exposición Profesional/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Adulto , Enfermedades de los Trabajadores Agrícolas/genética , Enfermedades de los Trabajadores Agrícolas/metabolismo , Brasil , Estudios de Casos y Controles , Cotinina/sangre , Femenino , Inestabilidad Genómica/efectos de los fármacos , Humanos , Masculino , Nicotina/metabolismo , Exposición Profesional/análisis , Oxidación-Reducción , Estrés Oxidativo/genética , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Nicotiana/metabolismo , Adulto JovenRESUMEN
Reperfusion injury following acute myocardial infarction is associated with significant morbidity. Activation of neuronal or non-neuronal cholinergic pathways in the heart has been shown to reduce ischemic injury and this effect has been attributed primarily to muscarinic acetylcholine receptors. In contrast, the role of nicotinic receptors, specifically alpha-7 subtype (α7nAChR) in the myocardium remains unknown which offers an opportunity to potentially repurpose several agonists/modulators that are currently under development for neurologic indications. Treatment of ex vivo and in vivo rat models of cardiac ischemia/reperfusion (I/R) with a selective α7nAChR agonist (GTS21) showed significant increases in left ventricular developing pressure, and rates of pressure development without effects on heart rate. These positive functional effects were blocked by co-administration with methyllycaconatine (MLA), a selective antagonist of α7nAChRs. In vivo, delivery of GTS21 at the initiation of reperfusion, reduced infarct size by 42% (p<0.01) and decreased tissue reactive oxygen species (ROS) by 62% (p<0.01). Flow cytometry of MitoTracker Red stained mitochondria showed that mitochondrial membrane potential was normalized in mitochondria isolated from GTS21 treated compared to untreated I/R hearts. Intracellular ATP concentration in cultured cardiomyocytes exposed to hypoxia/reoxygenation was reduced (p<0.001), but significantly increased to normoxic levels with GTS21 treatment, and this was abrogated by MLA pretreatment. Activation of stress-activated kinases, JNK and p38MAPK, were significantly reduced by GTS21 in I/R. We conclude that targeting myocardial 17nAChRs in I/R may provide therapeutic benefit by improving cardiac contractile function through a mechanism that preserves mitochondrial membrane potential, maintains intracellular ATP and reduces ROS generation, thus limiting infarct size.
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Daño por Reperfusión Miocárdica/fisiopatología , Receptor Nicotínico de Acetilcolina alfa 7/fisiología , Adenosina Trifosfato/metabolismo , Animales , Animales Recién Nacidos , Línea Celular , Corazón/fisiología , Humanos , Masculino , Potencial de la Membrana Mitocondrial , Mitocondrias Cardíacas/fisiología , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Recently, research on mining microRNA (or miRNA) expression data has received a lot of attention, mainly because of its role in gene regulation. However, such type of data - usually saved in the form of microarrays - are very specific, because they contain only a small number of cases (often less than 100) compared with large number of attributes (equal to several hundreds or even tens of thousand). The small number of cases available during the learning process can cause instability of the newly created classifiers. Secondly, the huge number of attributes imposes the necessity of selecting only a few dominant attributes strongly correlated with the decision. Thus, an application of fundamental machine learning approaches of mining microarray data and its further classification is problematic or even could just fail.Thus, the main goal of our research is to develop the generalized algorithm of mining microarray data (including miRNA data sets), mainly to improve stability and, consequently, accuracy of classification for the newly created learning classifiers. The main concept of the novel approach is based on iteratively inducing many subsequent decision rule sets - called decision rule generations - instead of inducing only a single decision rule set, as it is done routinely. The decision rules have been chosen as the baseline classifiers of the newly developed LEMRG (Learning from Examples Module based on Rule Generations) algorithm mainly because the decision rule-based knowledge representation is easier for humans to comprehend, rather than other learning models. In our research we used a miRNA expression level learning data set describing 11 types of human cancers, while the testing data set contained poorly differentiated cases of only four types of cancers. As expected, our new classifiers - saved in the form of so-called cumulative decision rule sets - had better stability and accuracy of classification than single decision rule sets induced in the traditional manner. Furthermore, the LEMRG was compared with other machine learning models. It was proven that only 3 out of all 16 tested classifiers enabled so effective classification as our newly developed approach. Thus, using our cumulative set of decision rules, all cases of cancer from two selected concepts - colon and ovary - were correctly classified. Furthermore, we showed the role of these selected miRNAs as the potential biomarkers for diagnosis of tumors.A preliminary result of our research on decision rule generations was initially presented at the first International Conference of Digital Medicine and Medical 3D Printing (17-19.06.2016, Nanjing, China).
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Algoritmos , Minería de Datos , MicroARNs/análisis , Humanos , Análisis por MicromatricesRESUMEN
This paper presents a wireless fault detection system for industrial motors that combines vibration, motor current and temperature analysis, thus improving the detection of mechanical faults. The design also considers the time of detection and further possible actions, which are also important for the early detection of possible malfunctions, and thus for avoiding irreversible damage to the motor. The remote motor condition monitoring is implemented through a wireless sensor network (WSN) based on the IEEE 802.15.4 standard. The deployed network uses the beacon-enabled mode to synchronize several sensor nodes with the coordinator node, and the guaranteed time slot mechanism provides data monitoring with a predetermined latency. A graphic user interface offers remote access to motor conditions and real-time monitoring of several parameters. The developed wireless sensor node exhibits very low power consumption since it has been optimized both in terms of hardware and software. The result is a low cost, highly reliable and compact design, achieving a high degree of autonomy of more than two years with just one 3.3 V/2600 mAh battery. Laboratory and field tests confirm the feasibility of the wireless system.
RESUMEN
Nogalamycin is an anthracycline antitumor antibiotic, consisting of the aromatic aglycone attached with a nogalose and a nogalamine. At present, the biosynthesis pathway of nogalamycin, especially the glycosylation mechanism of the two deoxysugar moieties, had still not been extensively investigated in vivo. In this study, we inactivated the three glycotransferase genes in the nogalamycin-produced strain, and investigated the function of these genes by analyzing the metabolites profiles in the fermentation broth. The in-frame deletion of snogD and disruption of snogE abolished the production of nogalamycin completely, indicating that the gene products of snogD and snogE are essential to the biosynthesis of nogalamycin. On the other hand, in-frame deletion of snogZ does not abolish the production of nogalamycin, but production yield was reduced to 28% of the wild type, implying that snogZ gene may involved in the activation of other glycotransferases in nogalamycin biosynthesis. This study laid the foundation of modification of nogalamycin biosynthesis/production by genetic engineering methods.