RESUMO
Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) are common food-borne pahogens that cause food poisoning in humans. In this study, we developed a method for the simultaneous determination of S. typhimurium and S. aureus based on multiplex polymerase spiral reaction (m-PSR) and melting curve analysis. Two pairs of primers were designed specifically to target the conserved invA gene of S. typhimurium and nuc gene of S. aureus, and the nucleic acid amplification reaction was achieved under isothermal conditions in the same reaction tube for 40 min at 61 °C, melting curve analysis of the amplification product was carried out. The distinct mean melting temperature allowed simultaneous differentiation of the two target bacteria in the m-PSR assay. The limit of detection of S. typhimurium and S. aureus that could be detected simultaneously was 4.1 × 10-4 ng genomic DNA and 2 × 101 CFU/mL pure bacterial culture. Based on this method, analysis of artificially contaminated samples showed excellent sensitivity and specificity consistent with those of pure bacterial cultures. This method is rapid, simultaneous and promises to be a useful tool for the detection of food-borne pathogens in the food industry.
Assuntos
Salmonella typhimurium , Staphylococcus aureus , Humanos , Salmonella typhimurium/genética , Staphylococcus aureus/genética , Microbiologia de Alimentos , Técnicas de Amplificação de Ácido Nucleico , Sensibilidade e EspecificidadeRESUMO
Illustrating the molecular structure of metal nanoclusters with the protection of multiple ligands is a prerequisite to understand structure-property relationships of nano or bulk materials with hybrid interfaces. Reported herein is the synthesis, total structure and electronic structure analysis of a new Ag/Cu alloy nanocluster with triple-ligand protection. The cluster with the formula of Ag10Cu16(C8H9S)16(PPh3)4(CF3CO2)8 has been attained in one-pot in a simple way. X-ray single crystal analysis displays its unique metal framework and more importantly rich interface structures. The ligands of phosphine, thioate and carboxylic acid are coordinated to the surface of the cluster in distinctive modes. The electronic structure of the cluster has been revealed by density functional theory, showing that it is a 2-electron superatom with jellium configurations of 1S2. In good accordance with the closure of the geometric and electronic structures, the cluster exhibits moderate stability, which makes it a candidate for further application in many fields.
RESUMO
An acoustic absorption structure of a double-layer porous metal material with air layers is proposed. The Johnson-Champoux-Allard (JCA) model combined with the transfer matrix method (TMM) was used to establish the theoretical calculation model of the sound absorption coefficient (SAC). Meanwhile, the SAC between 500 and 6300 Hz were measured with an impedance tube. The errors between the theoretical and experimental values were compared to illustrate the good predictability of the theoretical model within the inverse estimations of the transport properties. The effects of the material placement order, material thickness, and cavity depth on the sound absorption performance from 200 to 5000 Hz were analyzed using the theoretical model. Further, a multi-objective function genetic algorithm was used to optimize the porous material's thickness and SAC to obtain an acoustic structure with a smaller thickness and higher sound absorption. A series of optimal solutions were obtained for acoustic structures with a total thickness of less than 70 mm. When the total thickness of the foam metal was 33.57 mm, the average SAC reached 0.853, which was significantly lower than the total thickness of the previous experiments. The multi-objective function genetic algorithm can provide a reliable solution for the optimal design of most sound-absorbing structures.
RESUMO
CONTEXT: Gallic acid (GA) and lecithin showed important roles in antioxidant and drug delivery, respectively. A complex synthesized from GA and soybean lecithin (SL-GAC), significantly improved bioavailability of GA and pharmacological activities. However, the antioxidant activity of SL-GAC and its effect on iron-overload-induced liver injury remains unexplored. OBJECTIVE: This study investigates the antioxidant properties of SL-GAC in vitro and in mice, and its remediating effects against liver injury by iron-overloaded. MATERIALS AND METHODS: In vitro, free radical scavenging activity, lipid peroxidation inhibition, and ferric reducing power of SL-GAC were measured by absorbance photometry. In vivo, C57BL/6J mice were randomized into 4 groups: control, iron-overloaded, iron-overloaded + deferoxamine, and iron-overloaded + SL-GAC. Treatments with deferoxamine (150 mg/kg/intraperitioneally) and SL-GAC (200 mg/kg/orally) were given to the desired groups for 12 weeks, daily. Iron levels, oxidative stress, and biochemical parameters were determined by histopathological examination and molecular biological techniques. RESULTS: In vitro, SL-GAC showed DPPH and ABTS free radicals scavenging activity with IC50 values equal to 24.92 and 128.36 µg/mL, respectively. In C57BL/6J mice, SL-GAC significantly reduced the levels of serum iron (22.82%), liver iron (50.29%), aspartate transaminase (25.97%), alanine transaminase (38.07%), gamma glutamyl transferase (42.11%), malondialdehyde (19.82%), total cholesterol (45.96%), triglyceride (34.90%), ferritin light chain (18.51%) and transferrin receptor (27.39%), while up-regulated the levels of superoxide dismutase (24.69%), and glutathione (11.91%). CONCLUSIONS: These findings encourage the use of SL-GAC to treat liver injury induced by iron-overloaded. Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.
Assuntos
Sobrecarga de Ferro , Hepatopatias , Camundongos , Animais , Lecitinas/metabolismo , Lecitinas/farmacologia , Lecitinas/uso terapêutico , Antioxidantes/uso terapêutico , Glycine max , Ácido Gálico/farmacologia , Desferroxamina/farmacologia , Desferroxamina/metabolismo , Desferroxamina/uso terapêutico , Camundongos Endogâmicos C57BL , Hepatopatias/tratamento farmacológico , Estresse Oxidativo , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Fígado , Ferro/metabolismo , Peroxidação de LipídeosRESUMO
Choline, as a precursor of glycine betaine (GB) and phospholipids, is known to play roles in plant tolerance to salt stress, but the downstream metabolic pathways regulated by choline conferring salt tolerance are still unclear for non-GB-accumulating species. The objectives were to examine how choline affects salt tolerance in a non-GB-accumulating grass species and to determine major metabolic pathways of choline regulating salt tolerance involving GB or lipid metabolism. Kentucky bluegrass (Poa pratensis) plants were subjected to salt stress (100 mM NaCl) with or without foliar application of choline chloride (1 mM) in a growth chamber. Choline or GB alone and the combined application increased leaf photochemical efficiency, relative water content and osmotic adjustment and reduced leaf electrolyte leakage. Choline application had no effects on the endogenous GB content and GB synthesis genes did not show responses to choline under nonstress and salt stress conditions. GB was not detected in Kentucky bluegrass leaves. Lipidomic analysis revealed an increase in the content of monogalactosyl diacylglycerol, phosphatidylcholine and phosphatidylethanolamine and a decrease in the phosphatidic acid content by choline application in plants exposed to salt stress. Choline-mediated lipid reprogramming could function as a dominant salt tolerance mechanism in non-GB-accumulating grass species.
Assuntos
Colina/metabolismo , Metabolismo dos Lipídeos , Poa/metabolismo , Plantas Tolerantes a Sal/metabolismo , Betaína/metabolismo , Colina/farmacologia , Colina/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Genes de Plantas/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/fisiologia , Folhas de Planta/metabolismo , Poa/efeitos dos fármacos , Poa/fisiologia , Estresse Salino , Tolerância ao Sal , Plantas Tolerantes a Sal/fisiologiaRESUMO
BACKGROUND: Seed dimorphism has been thought to be a bet-hedging strategy that helps plants survive in the disturbed environment and has been widely studied for its ecological adaptation mechanism. Many studies showed that seed-associated microorganisms play an important role in enhancing plant fitness, but information regarding endophytic bacteria associated with dimorphic seeds is limited. This study explores the influence of seed coat structure and seed phytochemical properties on the community composition and diversity of endophytic bacteria of dimorphic seeds of Suaeda glauca. In this study, we used 16S rRNA high-throughput gene sequencing method to compare the community composition and bacterial diversity between brown and black seeds of Suaeda glauca. RESULTS: A significant difference was observed in seed coat structure and phytochemical properties between brown and black seeds of S. glauca. Total 9 phyla, 13 classes, 31 orders, 53 families, 102 genera were identified in the dimorphic seeds. The dominant phyla were Proteobacteria, Firmicutes, and Actinobacteria. The results showed that seed dimorphism had little impact on the diversity and richness of endophytic bacterial communities but significantly differs in the relative abundance of the bacterial community between brown and black seeds. At the phylum level, Actinobacteria tend to be enriched significantly in brown seeds. At the genus level, Rhodococcus, Ralstonia, Pelomonas and Bradyrhizobium tend to be enriched significantly in brown seeds, while Marinilactibacillus was mainly found in black seeds. Besides, brown seeds harbored a large number of bacteria with plant-growth-promoting traits, whereas black seeds presented bacteria with enzyme activities (i.e., pectinase, cellulolytic and xylanolytic activities). CONCLUSION: The endophytic bacterial community compositions were significantly different between dimorphic seeds of Suaeda glauca, and play an important role in the ecological adaptation of dimorphic seeds by performing different biological function roles. The endophytic bacterial communities of the dimorphic seeds may be influenced mainly by the seed coat structureand partly by the seed phytochemical characteristics. These findings provide valuable information for better understanding of the ecological adaptation strategy of dimorphic seeds in the disturbed environment.
Assuntos
Bactérias/metabolismo , Chenopodiaceae/microbiologia , Endófitos/metabolismo , Plantas Tolerantes a Sal/microbiologia , Sementes/microbiologia , Bactérias/genética , Biodiversidade , RNA Ribossômico 16S/genéticaRESUMO
LncRNA COL1A2-AS1 has been demonstrated to inhibit fibroblast proliferation of hypertrophic scars. However, the function of COL1A2-AS1 in normal skin fibroblasts remains poorly studied. Here, we report that overexpression of COL1A2-AS1 promoted normal skin fibroblast apoptosis. On the basis of mRNA-seq data and gene set enrichment analysis plus Kyoto encyclopedia of genes and genomes pathway analysis, 16 upregulated and 125 downregulated mRNAs were found; TGF-ß, Wnt, and MAPK pathways were potentially involved. Western blot assay confirmed that overexpression of COL1A2-AS1 repressed p-Smad3 expression and promoted ß-catenin expression. Furthermore, COL1A2-AS1 overexpression combined with either TGF-ß1 or siRNA against ß-catenin reversed the upregulation of apoptosis in the COL1A2-AS1 overexpression group. In conclusion, our study revealed the roles of COL1A2-AS1 in normal skin fibroblast apoptosis, with COL1A2-AS1 functioning by repressing p-Smad3 expression and promoting ß-catenin expression.
Assuntos
Colágeno Tipo I/metabolismo , Fibroblastos/metabolismo , RNA Longo não Codificante/fisiologia , Proteína Smad3/metabolismo , beta Catenina/metabolismo , Apoptose , Movimento Celular , Proliferação de Células , Células Cultivadas , Regulação para Baixo , Humanos , Regulação para CimaRESUMO
BACKGROUND: Currently, no available coherent management protocol exists for pediatric cancers associated with pleural effusion, ascites, and pericardial effusion. This study aimed to retrospectively present our experience in treating pediatric cancer patients with pleural effusion, ascites, and pericardial effusion using interleukin-2 (IL-2) and dexamethasone (DEX) intracavitary injections. METHODS: Between January 1st, 2008 and December 31st, 2020, medical reports of patients diagnosed with solid tumors or lymphoma were checked to identify patients diagnosed with > 2 cm pleural effusion, and/or more than grade 1 ascites, and/or more than small pericardial effusion. Patients diagnosed with effusions and treated with IL-2 and DEX were identified as being in the effusion group. Meanwhile, patients with the same primary tumors and effusions but did not receive interleukin 2 and DEX injection were reviewed and classified as the control group. RESULTS: Forty patients with solid tumors and 66 patients with lymphoma were further diagnosed with pleural effusion, ascites, or pericardial effusion. A total of 85 patients received IL-2 and DEX injection while the remaining 21 did not. The Kaplan Meier analysis revealed a significant difference between the two groups, with p < 0.01 for event free survival (EFS) and p < 0.01 for overall survival (OS), both of which had p < 0.01. Hazard ratio was found to be 0.344 for OS and 0.352 for EFS. CONCLUSIONS: This retrospective study illustrates that thoracic, intraperitoneal, or pericardial intracavitary injection of DEX plus IL-2 can be an effective and safe treatment for pediatric cancers with pleural effusion, ascites, and pericardial effusion.
Assuntos
Dexametasona/uso terapêutico , Interleucina-2/metabolismo , Linfoma/tratamento farmacológico , Derrame Pleural Maligno/tratamento farmacológico , Criança , Pré-Escolar , Estudos de Coortes , Dexametasona/farmacologia , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
A Gram-stain-positive, non-motile and coccus-shaped bacterium, designated strain LNNU 331112T, was isolated from the composite rhizosphere soil of the halophyte Suaeda aralocaspica (Bunge) Freitag and Schütze, which was collected in Xinjiang, north-west China. Growth occurred at 10-45 °C, pH 6.0-11.0 and in the presence of 0-10â% NaCl (w/v). Phylogenetic analysis based on the 16S rRNA gene sequence suggested that strain LNNU 331112T belonged to the genus Hoyosella and showed 95.6, 95.5 and 95.4â% sequence similarities to Hoyosella altamirensis DSM 45258T, Hoyosella subflava CGMCC 4.3532T and Hoyosella rhizosphaerae CGMCC 1.15478T, respectively. The estimated digital DNA-DNA hybridization relatedness values between strain LNNU 331112T and the type strains of H. altamirensis DSM 45258T, H. subflava CGMCC 4.3532T and H. rhizosphaerae CGMCC 1.15478T were 18.9, 19.3 and 18.3â%, respectively. The average nucleotide identity values between strain LNNU 331112T and H. altamirensis DSM 45258T, H. subflava CGMCC 4.3532T and H. rhizosphaerae CGMCC 1.15478T were 72.6, 72.7 and 72.3â%, respectively. The genome sequence of strain LNNU 331112T showed 69.0-72.3â% average amino acid identity values in comparison with the related genome sequences of three validly published Hoyosella species. The genome of strain LNNU 331112T was 3.47 Mb, with a DNA G+C content of 68.4 mol%. A total of 3182 genes were identified as protein-coding in strain LNNU 331112T. Genomic analysis revealed that a number of genes involved in osmotic pressure regulation, intracellular pH homeostasis and potassium (K+) uptake protein were found in strain LNNU 331112T. The predominant menaquinones were MK-8 (44.6â%) and MK-7 (55.4â%), which differentiated strain LNNU 331112T from other three recognized Hoyosella species. Major fatty acids (>10â%) were C17â:â1 ω8c (33.8â%), C16â:â0 (23.3â%), C17â:â0 (12.8â%) and summed feature 3 (12.9â%), which also clearly separated strain LNNU 331112T from three recognized Hoyosella species. The polar lipid profile of strain LNNU 331112T included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, one unidentified glycolipid, one unidentified phospholipid and two unidentified lipids. According to the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain LNNU 331112T is considered to represent a novel species of the genus Hoyosella, for which the name Hoyosella suaedae sp. nov. is proposed. The type strain is LNNU 331112T (=KCTC 39808T=CGMCC 1.17107T=DSM 103463T).
Assuntos
Chenopodiaceae , Mycobacteriaceae/classificação , Filogenia , Rizosfera , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , Chenopodiaceae/microbiologia , China , DNA Bacteriano/genética , Ácidos Graxos/química , Mycobacteriaceae/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
OBJECTIVE: To review the pharmacological characteristics, clinical evidence, and place in therapy of satralizumab for the treatment of neuromyelitis optica spectrum disorders (NMOSDs). DATA SOURCES: A comprehensive literature search was conducted in PubMed (January 2000 to October 15, 2020). Key search terms included satralizumab and neuromyelitis optica spectrum disorders. Other sources were derived from product labeling and ClinicalTrials.gov. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were reviewed and evaluated. Phase I, II, and III clinical trials were included. DATA SYNTHESIS: NMOSD is an autoimmune disease characterized by inflammatory lesions in the optic nerves and spinal cord. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. Phase III trials showed that protocol-defined relapse was 30% for satralizumab and 50% for placebo (P = 0.018) when patients with NMOSD were treated with satralizumab monotherapy; protocol-defined relapse was 20% for satralizumab and 43% for placebo (P = 0.02) when satralizumab was added to immunosuppressant treatment. Satralizumab is generally well tolerated, with common adverse effects including injection-related reaction. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Satralizumab has the potential to become a valuable treatment option for patients with NMOSD. CONCLUSION: Satralizumab appears to be safe and effective as monotherapy or in combination with an immunosuppressant for patients with NMOSD and has the potential to become a valuable treatment option for these patients.
Assuntos
Doenças Autoimunes , Neuromielite Óptica , Anticorpos Monoclonais Humanizados/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Neuromielite Óptica/tratamento farmacológicoRESUMO
BACKGROUND: Anti-synthetase syndrome (ASSD) is a chronic autoimmune condition characterized by antibodies directed against an aminoacycl transfer RNA synthetase (ARS) along with a group of clinical features including the classical clinical triad: inflammatory myopathy, arthritis, and interstitial lung disease (ILD). ASSD is highly heterogenous due to different organ involvement, and ILD is the main cause of mortality and function loss, which presents as different patterns when diagnosed. We designed this retrospective cohort to describe the clinical features and disease behaviour of ASSD associated ILD. METHODS: Data of 108 cases of ASSD associated ILD were retrospectively collected in Beijing Chaoyang Hospital from December 2017 to March 2019. Data were obtained from the Electronic Medical Record system. Patients were divided into 5 groups according to distinct aminoacyl tRNA synthetase (ARS) antibodies. RESULTS: Overall, 108 consecutive patients were recruited. 33 were JO-1 positive, 30 were PL-7 positive, 23 were EJ positive, 13 were PL-12 positive and 9 were OJ positive. The JO-1 (+) group had a significant higher rate of mechanic's hand (57.6%) than other 4 groups. Polymyositis/dermatomyositis (PM/DM) was diagnosed in 25 (23.1%) patients and no difference was observed among the 5 groups. The PL-7 (+) group had a higher frequency of UIP pattern (13.3%) than the other 4 groups but the difference was not significant, and the EJ (+) group had the most frequent OP pattern (78.2%), which was significantly higher than the PL-7 (+) (P < 0.001) and PL-12 (+) groups (P = 0.025). The median follow-up time was 10.7 months, during which no patients died. All received prednisone treatment, with or without immunosuppressants. At the 6-month follow-up, 96.3% of all patients (104/108) had a positive response to therapy, the JO-1 (+) and EJ (+) groups had a significantly higher improvement of forced vital capacity than the other 3 groups (P < 0.05), and the PL-7 group had the lowest FVC improvement (P < 0.05). The JO-1 (+) group and EJ (+) group had significantly higher anti-Ro-52 positive occurrence than the other 3 groups (P < 0.05). CONCLUSION: Anti PL-7 antibody had the same frequency as anti-JO-1 in ASSD-ILD, in which the ILD pattern was different with distinct anti-ARS antibodies. Most ASSD-ILD had a positive response to steroid therapies, with or without immunosuppressants. The PL-7 (+) group had the highest occurrence of UIP pattern, and a significantly lower response to therapy.
Assuntos
Autoanticorpos/imunologia , Dermatomiosite/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Miosite/fisiopatologia , Adulto , Idoso , Alanina-tRNA Ligase/imunologia , Anticorpos Antinucleares/imunologia , China , Estudos de Coortes , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Feminino , Glucocorticoides/uso terapêutico , Glicina-tRNA Ligase/imunologia , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/fisiopatologia , Imunossupressores/uso terapêutico , Isoleucina-tRNA Ligase/imunologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Miosite/tratamento farmacológico , Miosite/imunologia , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Treonina-tRNA Ligase/imunologia , Resultado do Tratamento , Capacidade VitalRESUMO
Choline may affect salt tolerance by regulating lipid and glycine betaine (GB) metabolism. This study was conducted to determine whether alteration of lipid profiles and GB metabolism may contribute to choline regulation and genotypic variations in salt tolerance in a halophytic grass, seashore paspalum (Paspalum vaginatum). Plants of Adalayd and Sea Isle 2000 were subjected to salt stress (200-mM NaCl) with or without foliar application of choline chloride (1 mM). Genotypic variations in salt tolerance and promotive effects of choline application on salt tolerance were associated with both the up-regulation of lipid metabolism and GB synthesis. The genotypic variations in salt tolerance associated with lipid metabolism were reflected by the differential accumulation of phosphatidylcholine and phosphatidylethanolamine between Adalayd and Sea Isle 2000. Choline-induced salt tolerance was associated with of the increase in digalactosyl diacylglycerol (DGDG) content including DGDG (36:4 and 36:6) in both cultivars of seashore paspalum and enhanced synthesis of phosphatidylinositol (34:2, 36:5, and 36:2) and phosphatidic acid (34:2, 34:1, and 36:5), as well as increases in the ratio of digalactosyl diacylglycerol: monogalactosyl diacylglycerol (DGDG:MGDG) in salt-tolerant Sea Isle 2000. Choline regulation of salt tolerance may be due to the alteration in lipid metabolism in this halophytic grass species.
Assuntos
Betaína/metabolismo , Colina/farmacologia , Metabolismo dos Lipídeos/fisiologia , Paspalum/metabolismo , Tolerância ao Sal/efeitos dos fármacos , Plantas Tolerantes a Sal/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Paspalum/genética , Desenvolvimento Vegetal , Folhas de Planta/genética , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Estresse Salino , Tolerância ao Sal/genética , Espectrometria de Massas em TandemRESUMO
The value of fractional exhaled nitric oxide (FeNO) in patients with chronic obstructive pulmonary disease (COPD) remains unclear. We aimed to assess whether FeNO is a more valuable biomarker than blood eosinophil count for identifying clinical characteristics of COPD. Stable COPD patients (n = 390) were included and stratified by FeNO and blood eosinophil counts at recruitment. The demographic characteristics, lung functions, St George Respiratory Questionnaire (SGRQ), serum inhaled allergen-specific IgE and the exacerbations in the preceding 12 months were compared. Risk factors for moderate or severe exacerbation in the preceding 12 months were examined by binary regression analysis. The cross-sectional study showed that 167 patients had high level of FeNO (≥25 ppb) and 223 in low level (<25 ppb), while 138 patients had high blood eosinophil count (≥200 cells/µL) and 252 had low (<200 cells/µL). Compared with the high FeNO group, there were higher proportion of patients with GOLD III-IV, higher SGRQ scores, more exacerbations in the preceding 12 months, and with lower positive proportion of sIgE in the low FeNO group (p < 0.05 for all). However, these phenomena above were not associated with blood eosinophil count. Finally, high FeNO level was associated with a lower moderate or severe exacerbation in preceding 12 months (RR: 0.541 [95%CI 0.319-0.917], p = 0.023). In stable COPD patients, FeNO, but not blood eosinophil count was associated with the COPD severity and allergic airway inflammation. However, the role of FeNO in guiding personalized treatment of COPD patients need to be further investigated.
Assuntos
Eosinófilos , Óxido Nítrico/análise , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Exacerbação dos Sintomas , Idoso , Biomarcadores/análise , Testes Respiratórios , Estudos Transversais , Feminino , Humanos , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/sangue , Índice de Gravidade de DoençaRESUMO
The classic NLRP3 inflammasome and NF-κB molecular pathways are activated in many inflammatory-related diseases, such as pleurisy. Because oridonin (Ori) has been indicated as a covalent NLRP3 inhibitor with strong anti-inflammasome activity, we herein aimed to assess the effects of Ori in a mouse model of carrageenan (CAR)-induced pleurisy. The results showed that CAR caused hemorrhaging and exudation of lung tissues and the release of inflammatory factors (TNF-α, IL-6 and IL-1ß), effects that were significantly reduced by treatment with Ori. In addition, increased neutrophil infiltration, protein concentrations and volumes were found in the exudates of the CAR group, and these phenomena were suppressed by Ori treatment. Regarding cellular pathways, Ori could alleviate the CAR-activated NF-κB and TXNIP/NLRP3 pathways. Additionally, oxidative stress was shown to be involved in the pathogenesis of pleurisy, but possible mechanisms remain to be explored. Herein, Ori reversed the CAR-induced depletion of GSH and SOD and the CAR-induced increases in ROS, MPO and MDA levels. Furthermore, Ori inhibited NOX-4 levels, initiated the dissociation of KEAP-1 from Nrf2, activated the downstream genes HO-1 and exerted antioxidative effects on CAR-induced pleurisy. In conclusion, Ori conferred protection against CAR-induced pleurisy via Nrf2-dependent antioxidative and NLRP3-dependent anti-inflammatory properties.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Diterpenos do Tipo Caurano/farmacologia , Pleurisia/prevenção & controle , Animais , Carragenina , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Feminino , Inflamassomos/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pleurisia/patologia , Tiorredoxinas/metabolismoRESUMO
Soil salinity poses a serious threat to alfalfa ( Medicago sativa L.) productivity. To characterize the molecular mechanisms of salinity tolerance in Medicago, the comparative proteome of leaves from Medicago sativa cv. Zhongmu No.1 (ZM1, salt-tolerant) and Medicago truncatula cv. Jemalong A17 (A17, salt-sensitive) was performed using the iTRAQ approach. A total of 438 differentially expressed proteins (DEPs) were identified, among which 282 and 120 DEPs were specific to A17 and ZM1, respectively. In salt-tolerant ZM1, key DEPs were primarily enriched in antioxidant system, starch and sucrose metabolism, and secondary metabolism. ZM1 possessed a greater ability to remove reactive oxygen species and methylglyoxal under salt stress, as demonstrated by enhancement of the antioxidant system and secondary metabolism. Moreover, ZM1 orchestrated starch and sucrose metabolism to accumulate various soluble sugars (sucrose, maltose, glucose, and trehalose), which in turn facilitate osmotic homeostasis. Salt stress dramatically inhibited photosynthesis of A17 due to the downregulation of the light-harvesting complex and photosystem II related protein. Quantitative analyses of photochemical efficiency, antioxidant enzyme activities, hydrogen peroxide, malondialdehyde, and soluble sugar contents were consistent with the alterations predicted on the basis of DEP functions. These results shed light on our understanding of the mechanisms underlying the salt tolerance of alfalfa.
Assuntos
Antioxidantes/metabolismo , Medicago sativa/fisiologia , Folhas de Planta/fisiologia , Proteômica/métodos , Tolerância ao Sal/efeitos dos fármacos , Açúcares/metabolismo , Antioxidantes/farmacologia , Metabolismo dos Carboidratos , Medicago sativa/metabolismo , Fotossíntese/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Especificidade da Espécie , Açúcares/farmacologiaRESUMO
Myocardial ischemia-reperfusion injury (MIRI) is a major cause of cardiovascular disease, leading to mortality and disability associated with coronary occlusion worldwide. A correlation of mammalian target of rapamycin (mTOR)/nuclear factor-kappa B (NF-κB) signaling pathway has been observed with brain damage resulting from myocardial ischemia. Therefore, by establishing MIRI rat model, this study aimed to explore whether ring finger protein 182 (RNF182) regulates the mTOR signaling pathway affecting MIRI. Initially, MIRI rat model was successfully established, followed by either treatment of shRNF182 or phosphoesterase (PITE) (inhibitor of the mTOR signaling pathway). Then, the serum levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP), and left ventricular end-diastolic pressure (LVEDP) were determined, followed by detection of myocardial infarct sizes and myocardial cell apoptosis. Moreover, the levels of related genes/proteins were determined to further determine the mechanisms of RNF182 in MIRI. First, RNF182 was upregulated in MIRI. Another key observation of this study was that rats with shRNF182 presented with downregulated SOD, GSH-Px, and MDA in serum, accompanied by decreased levels of LVEF, LVFS, LVSP, and LVEDP. In addition, both reduced myocardial infarct sizes and apoptosis of myocardial cells were observed after silencing RNF182. Furthermore, silencing of the RNF182 was observed to downregulate Bcl 2-associated X and cysteine proteinase 3 but upregulate mTOR, ribosome protein subunit 6 kinase 1, eukaryotic elongation factor 2, and B-cell lymphoma-2. Importantly, the effects of RNF182 silencing were reversed after PITE treatment. In conclusion, our study demonstrates that RNF182 silencing can prevent ventricular remodeling in rats after MIRI by activating the mTOR signaling pathway.
RESUMO
Abscisic acid (ABA) may play roles in mediating cross stress tolerance in plants. The objectives of this study were to investigate the priming effects of drought and ABA on heat tolerance and to determine how ABA may be involved in enhanced heat tolerance by drought. Focusing on the transcriptional level, two independent experiments were conducted, using a perennial grass species, tall fescue (Festuca arundinacea) and Arabidopsis. In experiment 1, tall fescue plants were exposed to mild drought by withholding irrigation for 8 days (drought priming) and foliar sprayed with ABA or an ABA-synthesis inhibitor (fluridone). After that they were subsequently subjected to heat stress (38/33°C day/night) for 25 days in growth chambers. In experiment 2, Arabidopsis Columbia ecotype (wild-type) and ABA-deficient mutant (aba3-1, CS157) were pre-treated with drought priming and then exposed to heat stress (45/40°C) for 3 days. The physiological analysis demonstrated that both drought priming and foliar application of ABA-enhanced heat tolerance in tall fescue, while drought priming had no significant effects on heat tolerance in ABA-deficient Arabidopsis plants. Application of fluridone to tall fescue and ABA-deficient mutants of Arabidopsis exhibited diminished or attenuated positive effects of drought priming on heat tolerance. ABA mediation of acquired heat tolerance by drought priming was associated with the upregulation of CDPK3, MPK3, DREB2A, AREB3, MYB2, MYC4, HsfA2, HSP18, and HSP70. Our study revealed the roles of ABA in drought priming-enhanced heat tolerance, which may involve transcriptional regulation for stress signaling, ABA responses and heat protection.
Assuntos
Ácido Abscísico/metabolismo , Arabidopsis/fisiologia , Secas , Festuca/fisiologia , Estresse Fisiológico , Termotolerância , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Temperatura AltaRESUMO
BACKGROUND: Alfalfa (Medicago sativa L.), the primary forage crop throughout the world, is sensitive to salt stress during the germination stage. To investigate the response of alfalfa to salt stress, a comprehensive proteomic analysis was performed comparing alfalfa cultivars that differ in salinity tolerance in the early seedling. RESULTS: Five cultivars were examined for salt tolerance, and the most salt-tolerant cultivar, ZhongmuNo.3, and the most salt-sensitive cultivar, Daxiyang, were compared in terms of their physiological and proteomic responses. The two alfalfa cultivars seeds were exposed to 0 mmolL-1 or 200 mmolL-1 NaCl salt treatment for 10 days. Salt stress significantly reduced young seedling growth and the cotyledons' chlorophyll content; meanwhile, it increased the cotyledons' H2 O2 and malondialdehyde (MDA) levels, all of which were less adversely affected in ZhongmuNo.3 than in Daxiyang. A total of 51 spots (24 and 27 protein spots in the salt-sensitive and salt-tolerant cultivars, respectively) were identified as significantly differentially expressed using two-dimensional electrophoresis analysis. The proteins that were associated with salt tolerance included antioxidants/detoxifying enzymes, molecular chaperones, energy metabolic enzymes, a secondary metabolic enzyme, and pathogenesis-related proteins. CONCLUSIONS: Under salt stress, ZhongmuNo.3 possessed a higher capacity for reactive oxygen species (ROS) scavenging, a more abundant energy supply, and stronger photosynthesis than the salt-sensitive cultivar Daxiyang, and these physiological processes may be the primary contributors to salt tolerance in ZhongmuNo.3. These advanced proteome data expand our knowledge of the physiology of the response of alfalfa to salt stress, providing a potentially valuable foundation for molecular breeding to enhance salt tolerance. © 2018 Society of Chemical Industry.
Assuntos
Medicago sativa/metabolismo , Sementes/crescimento & desenvolvimento , Cloreto de Sódio/metabolismo , Clorofila/metabolismo , Germinação , Malondialdeído/metabolismo , Medicago sativa/química , Medicago sativa/genética , Medicago sativa/crescimento & desenvolvimento , Fotossíntese , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteômica , Espécies Reativas de Oxigênio/metabolismo , Tolerância ao Sal , Plântula/química , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Sementes/química , Sementes/genética , Sementes/metabolismoRESUMO
Endogenous peptides recently attract increasing attention for their participation in various biological processes. Their roles in the pathogenesis of human hypertrophic scar remains poorly understood. In this study, we used liquid chromatography-tandem mass spectrometry to construct a comparative peptidomic profiling between human hypertrophic scar tissue and matched normal skin. A total of 179 peptides were significantly differentially expressed in human hypertrophic scar tissue, with 95 upregulated and 84 downregulated peptides between hypertrophic scar tissue and matched normal skin. Further bioinformatics analysis (Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis) indicated that precursor proteins of these differentially expressed peptides correlate with cellular process, biological regulation, cell part, binding and structural molecule activity ribosome, and PPAR signaling pathway occurring during pathological changes of hypertrophic scar. Based on prediction database, we found that 78 differentially expressed peptides shared homology with antimicrobial peptides and five matched known immunomodulatory peptides. In conclusion, our results show significantly altered expression profiles of peptides in human hypertrophic scar tissue. These peptides may participate in the etiology of hypertrophic scar and provide beneficial scheme for scar evaluation and treatments.
Assuntos
Cicatriz Hipertrófica/metabolismo , Cicatriz/metabolismo , Peptídeos/metabolismo , Proteoma/metabolismo , Pele/metabolismo , Adulto , Cromatografia Líquida/métodos , Biologia Computacional/métodos , Feminino , Humanos , Proteômica/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
Endogenous peptides play crucial roles in various biological processes. Their effects on the pathogenesis of human infantile hemangioma remains poorly understood. In this study, we construct a comparative peptidomic profiling between human infantile hemangioma tissue and matched normal skin using liquid chromatography-tandem mass spectrometry. A total of 192 peptides were significantly differentially expressed in human infantile hemangioma tissue, with 182 upregulated, and 10 downregulated peptides between infantile hemangioma tissue and matched normal skin. Performing bioinformatics analysis (Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis), we found that precursor proteins of these differentially expressed peptides correlate with metabolic process, biological regulation, binding, catalytic activity, and pathways in cancer occurring during pathological changes of infantile hemangioma. Furthermore, 89 differentially expressed peptides shared homology with antimicrobial peptides and 13 matched known immunomodulatory peptides based on prediction database. In conclusion, our results reveal significantly altered expression profiles of peptides in human infantile hemangioma tissue. These peptides may participate in the etiology of infantile hemangioma and provide beneficial scheme for clinical treatments.