RESUMO
BACKGROUND: Red blood cells (RBCs) transfusion is related to perioperative neurocognitive disorders. The toxic effect of free heme has been identified in many pathologies. However, the underlying mechanisms of RBCs transfusion or free heme in cognitive impairment have not been clearly explored. Therefore, this research was conducted to determine the mechanism of free heme-induced neuroinflammation and cognitive impairment. METHODS: Rats were received intraperitoneal injection of hemin alone or combined with intracerebroventricular injection of Hemopexin (HPX), and MWM test was conducted to measure cognitive function. The amount of heme-HPX complexes was evaluated by flow cytometry for CD91 + cells. The microglial inflammatory response in rat brain was observed by immunofluorescence staining of Iba-1, and the inflammatory factors of TNF-α, IL-1ß and IL-6 in rat brain and BV2 cells were detected by ELISA analysis. Furthermore, neuronal apoptosis in HT22 cells alone and in HT22 + BV2 coculture system was detected by flow cytometry and immunofluorescence staining. Finally, western blot was conducted to detect TLR4/MyD88/NF-κB proteins in rat brain and BV2 cells treated with hemin or combined with pathway inhibitors. Additionally, the M1 surface marker CD86 was observed in BV2 cells to further confirm neuroinflammation. RESULTS: Intraperitoneal injection of hemin induced cognitive impairment, increase of CD91 + cells, up-regulation of TNF-α and IL-1ß, down-regulation of IL-6, activation of microglia, and activation of the TLR4/MyD88/NF-κB signaling pathway in rat brain. Significantly, intracerebroventricular injection of HPX reduced the above effects. Hemin induced boost of TNF-α, IL-1ß and IL-6 in BV2 cells, as well as apoptosis in HT22 cells. Notably, when HT22 cells were cocultured with BV2 cells, apoptosis was significantly increased. Hemin also induced activation of the TLR4/MyD88/NF-κB signaling pathway and increased the M1 surface marker CD86 in BV2 cells, and inhibiting this pathway reduced the inflammatory responses. CONCLUSIONS: Free heme induces cognitive impairment, and the underlying mechanism may involve neuronal apoptosis and microglial inflammation via the TLR4/MyD88/NF-κB signaling pathway. HPX may have potential therapeutic effects. Video Abstract.
Assuntos
Disfunção Cognitiva , NF-kappa B , Animais , Ratos , Heme , Microglia , Fator 88 de Diferenciação Mieloide , Hemina/farmacologia , Doenças Neuroinflamatórias , Interleucina-6 , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa , Proteínas Adaptadoras de Transdução de Sinal , Disfunção Cognitiva/induzido quimicamente , Transdução de SinaisRESUMO
The primary aim of this research was to explore the functions of Wtap and Ythdf1 in regulating neuronal Lipocalin-2 (Lcn2) through m6A modification in traumatic brain injury (TBI). By employing transcriptome sequencing and enrichment analysis, we identified the Wtap/Ythdf1-mediated Lcn2 m6A modification pathway as crucial in TBI. In our in vitro experiments using primary cortical neurons, knockout of Wtap and Ythdf1 led to the inhibition of Lcn2 m6A modification, resulting in reduced neuronal death and inflammation. Furthermore, overexpression of Lcn2 in cortical neurons induced the activation of reactive astrocytes and M1-like microglial cells, causing neuronal apoptosis. In vivo experiments confirmed the activation of reactive astrocytes and microglial cells in TBI and importantly demonstrated that Wtap knockdown improved neuroinflammation and functional impairment. These findings underscore the significance of Wtap/Ythdf1-mediated Lcn2 regulation in TBI secondary injury and suggest potential therapeutic implications for combating TBI-induced neuroinflammation and neuronal damage.
Assuntos
Lesões Encefálicas Traumáticas , Lipocalina-2 , Neurônios , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Lipocalina-2/metabolismo , Lipocalina-2/genética , Animais , Neurônios/metabolismo , Neurônios/patologia , Camundongos , Microglia/metabolismo , Microglia/patologia , Astrócitos/metabolismo , Astrócitos/patologia , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Masculino , Camundongos Endogâmicos C57BL , Apoptose , Camundongos Knockout , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologiaRESUMO
BACKGROUND: Systemic Inflammatory Response Index (SIRI), a composite inflammatory marker encompassing neutrophils, monocytes, and lymphocytes, has been recognized as a reliable marker of systemic inflammation. This article undertakes an analysis of clinical data from ST-segment Elevation Myocardial Infarction (STEMI) patients, aiming to comprehensively assess the relationship between SIRI, STEMI, and the degree of coronary stenosis. METHODS: The study involved 1809 patients diagnosed with STEMI between the years 2020 and 2023. Univariate and multivariate logistic regression analyses were conducted to evaluate the risk factors for STEMI. Receiver operating characteristic (ROC) curves were generated to determine the predictive power of SIRI and neutrophil-to-lymphocyte ratio (NLR). Spearman correlation analysis was performed to assess the correlation between SIRI, NLR, and the Gensini score (GS). RESULTS: Multivariate logistic regression analysis showed that the SIRI was the independent risk factor for STEMI (adjusted odds ratio (OR) in the highest quartile = 24.96, 95% confidence interval (CI) = 15.32-40.66, P < 0.001). In addition, there is a high correlation between SIRI and GS (ß:28.54, 95% CI: 24.63-32.46, P < 0.001). The ROC curve analysis was performed to evaluate the predictive ability of SIRI and NLR for STEMI patients. The area under the curve (AUC) for SIRI was 0.789. The AUC for NLR was 0.754. Regarding the prediction of STEMI in different gender groups, the AUC for SIRI in the male group was 0.771. The AUC for SIRI in the female group was 0.807. Spearman correlation analysis showed that SIRI exhibited a stronger correlation with GS, while NLR was lower (SIRI: r = 0.350, P < 0.001) (NLR: r = 0.313, P < 0.001). CONCLUSION: The study reveals a strong correlation between the SIRI and STEMI as well as the degree of coronary artery stenosis. In comparison to NLR, SIRI shows potential in predicting acute myocardial infarction and the severity of coronary artery stenosis. Additionally, SIRI exhibits a stronger predictive capability for female STEMI patients compared to males.
Assuntos
Estenose Coronária , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Feminino , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Estudos Transversais , Contagem de Linfócitos , Linfócitos , Neutrófilos , Estenose Coronária/diagnóstico por imagem , Síndrome de Resposta Inflamatória Sistêmica , Estudos RetrospectivosRESUMO
BACKGROUND: Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. METHODS: Pediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. RESULTS: In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively (P = 0.021). CONCLUSIONS: The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry- ChiCTR2300073879 (24/07/2023).
Assuntos
Analgesia Controlada pelo Paciente , Hidromorfona , Ketamina , Humanos , Criança , Estudos Prospectivos , Analgesia Controlada pelo Paciente/efeitos adversos , Dor Pós-Operatória/etiologia , AnalgésicosRESUMO
BACKGROUND: Cold chain distribution with multiple links maintains low temperatures to ensure the quality of meat products, whereas temperature fluctuations during this are often disregarded by the industry. The present study simulated two distinct temperatures cold chain distribution processes. Quality indicators and high-throughput sequencing were employed to investigate the effects of temperature fluctuations on the quality and microbial diversity of beef meatballs during cold chain distribution. RESULTS: Quality indicators revealed that temperature fluctuations during simulated cold chain distribution significantly (P < 0.05) exacerbated the quality deterioration of beef meatballs. High-throughput sequencing demonstrated that temperature fluctuations affected the diversity and structure of microbial community. Lower microbial species abundance and higher microbial species diversity were observed in the temperature fluctuations group. Proteobacteria and Pseudomonas were identified as the dominant phylum and genus in beef meatballs, respectively, exhibiting faster growth rates and greater relative abundance under temperature fluctuations. CONCLUSION: The present study demonstrates that temperature fluctuations during simulated cold chain distribution can worsen spoilage and shorten the shelf life of beef meatballs. It also offers certain insights into the spoilage mechanism and preservation of meat products during cold chain distribution. © 2024 Society of Chemical Industry.
Assuntos
Bactérias , Temperatura Baixa , Armazenamento de Alimentos , Produtos da Carne , Bovinos , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Produtos da Carne/microbiologia , Produtos da Carne/análise , Microbiologia de Alimentos , Microbiota , Conservação de Alimentos/métodos , Temperatura , BiodiversidadeRESUMO
O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant genetic disorder caused by mutations in the KMT2E (lysine methyltransferase 2E) gene. The Third Xiangya Hospital of Central South University admitted a 12-year and 9-month-old male patient who presented with growth retardation, intellectual disability, and distinctive facial features. Peripheral blood was collected from the patient, and DNA was extracted for genetic testing. Chromosome karyotyping showed 46XY. Whole-exome sequencing and low-coverage massively parallel copy number variation sequencing (CNV-seq) revealed a 506 kb heterozygous deletion in the 7q22.3 region, which includes 6 genes, including KMT2E. The patient was diagnosed with ODLURO syndrome. Both the patient's parents and younger brother had normal clinical phenotypes and genetic test results, indicating that this deletion was a de novo mutation. The clinical and genetic characteristics of this case can help increase clinicians' awareness of ODLURO syndrome.
Assuntos
Deficiência Intelectual , Humanos , Masculino , Deficiência Intelectual/genética , Criança , Histona-Lisina N-Metiltransferase/genética , Mutação , Transtornos do Crescimento/genética , Anormalidades Múltiplas/genética , Cromossomos Humanos Par 7/genética , Cariotipagem , Fenótipo , Variações do Número de Cópias de DNA , Sequenciamento do Exoma , Heterozigoto , Contratura , Microcefalia , FáciesRESUMO
Deep oceans receive mercury (Hg) from upper oceans, sediment diagenesis, and submarine volcanism; meanwhile, sinking particles shuttle Hg to marine sediments. Recent studies showed that Hg in the trench fauna mostly originated from monomethylmercury (MMHg) of the upper marine photosynthetic food webs. Yet, Hg sources in the deep-sea chemosynthetic food webs are still uncertain. Here, we report Hg concentrations and stable isotopic compositions of indigenous biota living at hydrothermal fields of the Indian Ocean Ridge and a cold seep of the South China Sea along with hydrothermal sulfide deposits. We find that Hg is highly enriched in hydrothermal sulfides, which correlated with varying Hg concentrations in inhabited biota. Both the hydrothermal and cold seep biota have small fractions (<10%) of Hg as MMHg and slightly positive Δ199Hg values. These Δ199Hg values are slightly higher than those in near-field sulfides but are 1 order of magnitude lower than the trench counterparts. We suggest that deep-sea chemosynthetic food webs mainly assimilate Hg from ambient seawater/sediments and hydrothermal fluids formed by percolated seawater through magmatic/mantle rocks. The MMHg transfer from photosynthetic to chemosynthetic food webs is likely limited. The contrasting Hg sources between chemosynthetic and trench food webs highlight Hg isotopes as promising tools to trace the deep-sea Hg biogeochemical cycle.
Assuntos
Mercúrio , Poluentes Químicos da Água , Isótopos de Mercúrio/análise , Cadeia Alimentar , Monitoramento Ambiental , Mercúrio/análise , Isótopos , Oceano Índico , Biota , Poluentes Químicos da Água/análiseRESUMO
CO2 emissions are of global concern because of climate change. China has become the largest CO2 emitter in the world and presently accounts for 30% of global emissions. Here, we analyze the major drivers of energy-related CO2 emissions in China from 1978 when the reform and opening-up policy was launched. We find that 1) there has been a 6-fold increase in energy-related CO2 emissions, which was driven primarily (176%) by economic growth followed by population growth (16%), while the effects of energy intensity (-79%) and carbon intensity (-13%) slowed the growth of carbon emissions over most of this period; 2) energy-related CO2 emissions are positively related to per capita gross domestic product (GDP), population growth rate, carbon intensity, and energy intensity; and 3) a portfolio of command-and-control policies affecting the drivers has altered the total emission trend. However, given the major role of China in global climate change mitigation, significant future reductions in China's CO2 emissions will require transformation toward low-carbon energy systems.
RESUMO
The extractive industry consumes vast amounts of energy and is a major contributor to greenhouse gas (GHG) emissions. However, its climatic impacts have not yet been fully accounted for. In this study, we estimated the GHG emissions from extractive activities globally with a focus on China, and assessed the main emission drivers. In addition, we predicted the Chinese extractive industry emissions in the context of global mineral demand and cycling. As of 2020, GHG emissions from the global extractive industry had reached 7.7 billion tons of CO2 equivalents (CO2e), accounting for approximately 15.0% of the global anthropogenic GHG emissions (excluding GHG emissions from land use, land-use change, and forestry activities (LULUCF), with China being the largest emitter, accounting for 3.5% of global emissions. Extractive industry GHG emissions are projected to peak by 2030 or even earlier to achieve low-carbon peak targets. The most critical pathway for reducing GHG emissions in the extractive industry is to control emissions from coal mining. Therefore, reducing methane emissions from mining and washing coal (MWC) should be prioritized.
Assuntos
Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Efeito Estufa , Dióxido de Carbono/análise , Indústrias , CarbonoRESUMO
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which tumor-induced osteochondrosis is a metabolic bone disease caused by increased renal excretion of phosphorus due to excessive secretion of fibroblast growth factor 23 (FGF23) by tumor tissue. We report here a rare case of TIO in which the tumor was found in the hyoid body and the patient had tertiary hyperparathyroidism. The patient's symptoms did not improve after removal of the tumor from the hyoid body, and the patient's hypophosphatemia was gradually improved after subsequent removal of the left parathyroid gland. TIO derived from the tongue tumor is very rare, and also subsequent tertiary hyperparathyroidism is even rarer. This report helps to improve the understanding of TIO and provides reference in the diagnosis and treatment of TIO.
Assuntos
Hiperparatireoidismo , Osteomalacia , Síndromes Paraneoplásicas , Humanos , Síndromes Paraneoplásicas/etiologia , Osteomalacia/etiologia , Glândulas ParatireoidesRESUMO
BACKGROUND: Traumatic brain injury (TBI) is a kind of acquired brain injury, which is caused by external mechanical forces. Moreover, the neuroprotective role of sevoflurane (Sevo) has been identified in TBI. Therefore, this research was conducted to figure out the mechanism of Sevo in TBI via FGF2. METHODS: The key factors of neuroprotective effects of Sevo in TBI rats were predicted by bioinformatics analysis. A TBI model was induced on rats that then inhaled Sevo for 1 h and grouped via lentivirus injection. Modified Neurological Severity Score was adopted to evaluate neuronal damage in rats, followed by motor function and brain water content measurement. FGF2, EZH2, and HES1 expression in brain tissues was evaluated by immunofluorescence staining, and expression of related genes and autophagy factors by RT-qPCR and Western blot analysis. Methylation-specific PCR was performed to assess HES1 promoter methylation level, and ChIP assay to detect the enrichment of EZH2 in the HES1 promoter. Neuronal damage was assessed by cell immunofluorescence staining, and neuronal apoptosis by Nissl staining, TUNEL staining, and flow cytometry. RESULTS: Sevo diminished brain edema, improved neurological scores, and decreased neuronal apoptosis and autophagy in TBI rats. Sevo preconditioning could upregulate FGF2 that elevated EZH2 expression, and EZH2 bound to the HES1 promoter to downregulate HES1 in TBI rats. Also, FGF2 or EZH2 overexpression or HES silencing decreased brain edema, neurological deficits, and neuronal autophagy and apoptosis in Sevo-treated TBI rats. CONCLUSIONS: Our results provided a novel insight to the neuroprotective mechanism of Sevo in TBI rats by downregulating HES1 via FGF2/EZH2 axis activation.
Assuntos
Lesões Encefálicas Traumáticas , Fármacos Neuroprotetores , Animais , Apoptose , Lesões Encefálicas Traumáticas/metabolismo , Fator 2 de Crescimento de Fibroblastos , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Sevoflurano/farmacologia , Sevoflurano/uso terapêuticoRESUMO
Nanoparticles (NPs) promise to address current limitations for treating acute pancreatitis (AP) via inflammatory cell-mediated sequestration. However, very few studies have explored the influence of NP size on their behavior in different stages of AP. The present work investigated the biodistribution of IR780 loaded mesoporous silica nanoparticles (MSNs) with sizes of 60, 150 or 300 nm after intravenous administration to rats of mild AP (MAP) or severe AP (SAP). Four hours after administration, MSN150 was present to a much greater extent in the pancreas than MSN60 or MSN300, irrespective of disease severity. MSN150 was present to a lower extent in pancreas, intestine and ascites in SAP than MAP rats, indicating weaker passive targeting in SAP rats. This may reflect greater blood loss and slower blood flow in SAP. These findings may guide the rational engineering of NPs with respect to particle size and disease severity for AP therapy.
Assuntos
Nanopartículas/administração & dosagem , Nanopartículas/uso terapêutico , Pancreatite/tratamento farmacológico , Tamanho da Partícula , Dióxido de Silício/administração & dosagem , Doença Aguda , Administração Intravenosa , Animais , Masculino , Pâncreas/patologia , Pancreatite/patologia , Ratos , Ratos WistarRESUMO
Treatment-induced neuropathy is an distinct, acute form of neuropathic pain which often occur shortly after initiation of intensive glycemic control and is characterized by excruciating neuropathic pain. It is a rare form of diabetic neuropathy and easy to be misdiagnosed. Clinical characteristics were analyzed based on two cases of treatment-induced neuropathy in diabetes accepted by the Third Xiangya Hospital of Central South University. It is proposed that strict glycemic control may lead to the occurrence of the disease. At Present, the pathogenesis is still unclear. Besides, the morbidity is much higher than we expected. It is important to improve the doctors awareness of this disease and avoid the the disease through carful glycemic control.
Assuntos
Neuropatias Diabéticas , Neuralgia , Glicemia , Humanos , InsulinaRESUMO
Filamentous fungus F03 belonging to Basidiomycota was obtained and identified as Phlebiopsis crassa based on ITS sequence when Morchella. sp was isolated from the wild fruiting body by spores releasing method. Chemical constituents were separated by gel chromatography, HPLC and recrystallization. Structures of compounds were confirmed by NMR data. Four products orsellinic acid (1), α-nigerose (2), uridine (3), N-(4-hydroxyphenyl)acetamide (4) were identified and all compounds were isolated from the genus Phlebiopsis for the first time.
Assuntos
Basidiomycota/química , Cromatografia Líquida de Alta Pressão/métodos , Polyporales/químicaRESUMO
The water quality in drinking water source area is essential for human health. Due to rapid urbanization and industrialization, the pollutants, especially trace elements, are continuously discharged into aquatic environment and pose a risk to human health. An extensive investigation was carried out in drinking water source area in highly urbanized Tianjin of China. Long-term monitoring data of the water body was collected on conventional physical and chemical parameters (pH, ions, TOC etc.) and metallic elements (Hg, As Cd, Pb, Co, U etc.) from 2005 to 2017. Our results showed that CaMg-Cl-SO4 and CaMg-HCO3 were the two prominent hydrochemical materials, implying that the pollution of aquatic system was mainly caused by anthropogenic activities and mineral dissolution within terms of drinking water guidelines (national and international standards), the concentrations of arsenic (As) and iron (Fe) were beyond the quality standards. Multivariate statistical approaches were applied to assess the origins of the elements. The results showed that human activities, as well as endogenous release, contributed significantly to appearance of trace elements. A transformation from low-trophic state to high-trophic state was in progress from 2005 to 2017 in Yuqiao reservoir, and most of the water was not heavily polluted by trace elements. The health risk assessment suggested that As had the potential to cause carcinogenic harm to the local residents, with daily dietary ingestion as the most predominant pathway.
Assuntos
Água Potável/normas , Exposição Ambiental/análise , Monitoramento Ambiental , Água Doce/química , Água Subterrânea/química , Poluentes Químicos da Água/análise , China , Água Potável/química , Humanos , Medição de Risco , Oligoelementos/análise , UrbanizaçãoRESUMO
Previous studies have demonstrated that myeloid zinc finger 1 (MZF1) in the dorsal root ganglion (DRG) participates in neuropathic pain induced by chronic-constriction injury (CCI) via regulation of voltage-gated K+ channels (Kv). Emerging evidence indicates that transient receptor potential vanilloid 1 (TRPV1) is involved in the development and maintenance of neuropathic pain. Although it is known that the transcription of TRPV1 is regulated by Kruppel-like zinc-finger transcription factor 7 (Klf7)-and that the structure of TRPV1 is similar to that of Kv-few studies have systematically investigated the relationship between MZF1 and TRPV1 in neuropathic pain. In the present study, we demonstrated that CCI induced an increase in MZF1 and TRPV1 in lumbar-level 4/5 (L4/5) DRGs at 3 days post-CCI and that this increase was persistent until at least 14 days post-CCI. DRG microinjection of rAAV5-MZF1 into the DRGs of naïve rats resulted in a decrease in paw-withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared with that of the rAAV5-EGFP group, which started at four weeks and lasted until at least eight weeks after microinjection. Additionally, prior microinjection of MZF1 siRNA clearly ameliorated CCI-induced reduction in PWT and PWL at 3 days post-CCI and lasted until at least 7 days post-CCI. Correspondingly, microinjection of MZF1 siRNA subsequent to CCI alleviated the established mechanical allodynia and thermal hyperalgesia induced by CCI, which occurred at 3 days postinjection and lasted until at least 10 days postinjection. Microinjection of rAAV5-MZF1 increased the expression of TRPV1 in DRGs. Microinjection of MZF1 siRNA diminished the CCI-induced increase of TRPV1, but not P2X7R, in DRGs. These findings suggest that MZF1 may contribute to neuropathic pain via regulation of TRPV1 expression in DRGs.
Assuntos
Gânglios Espinais/metabolismo , Neuralgia/metabolismo , Limiar da Dor/fisiologia , Canais de Cátion TRPV/metabolismo , Transativadores/metabolismo , Animais , Gânglios Espinais/crescimento & desenvolvimento , Hiperalgesia/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , Ratos Sprague-DawleyRESUMO
BACKGROUND: BcGs1, a cell wall-degrading enzyme (CWDE), was originally derived from Botrytis cinerea. Our previous study revealed that BcGs1 could trigger defense responses and protect plants against various pathogens. We researched the defense response mechanism underlying this BcGs1 elicitation in tomato. RESULTS: We revealed that the two domains were required for BcGs1's full necrosis activity. According to analysis and quantitative real-time PCR of the up-regulated proteins and genes filtered by iTRAQ-based quantitative proteome approach, oxidative metabolism and phenylpropanoid metabolism were speculated to be involved in BcGs1-triggered defense response in tomato. Furthermore, experimental evidence showed that BcGs1 triggered reactive oxygen species (ROS) burst and increased the level of phenylalanine-ammonia lyase (PAL) and peroxidase (POD) enzyme activity, as well as lignin accumulation. Moreover, histochemical analysis revealed that infiltration of BcGs1 in tomato leaves exhibited cell wall thickening compared with untreated plants. CONCLUSIONS: The results suggested that BcGs1 activated the basal defense response included lignin metabolism contributed to BcGs1-induced resistance to Botrytis. cinerea infection in tomato.
Assuntos
Botrytis/enzimologia , Resistência à Doença , Glucana 1,4-alfa-Glucosidase/metabolismo , Lignina/metabolismo , Doenças das Plantas/imunologia , Solanum lycopersicum/imunologia , Botrytis/fisiologia , Parede Celular/metabolismo , Proteínas Fúngicas/metabolismo , Interações Hospedeiro-Patógeno , Peróxido de Hidrogênio/metabolismo , Solanum lycopersicum/metabolismo , Solanum lycopersicum/microbiologia , Peroxidase/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Propanóis/metabolismo , Domínios Proteicos , Espécies Reativas de Oxigênio/metabolismo , Metabolismo SecundárioRESUMO
Background: It has been demonstrated that upregulation of CXCL12 and CXCR4 in spinal cord involves in the pathogenesis of neuropathic, inflammatory, and cancer pain. However, whether CXCL12/CXCR4 signaling contributes to postsurgical pain remains unknown. The aim of the present study is to investigate the role of CXCL12/CXCR4 signaling in the genesis of postsurgical pain and the underlying mechanism. Results: Plantar incision in rat hind paw resulted in increased expressions of CXCL12 and CXCR4 in spinal dorsal horn. Double immunofluorescence staining revealed that CXCL12 expressed in neurons and astrocytes, and CXCR4 exclusively co-localized with neuronal cells. Prior administration of AMD3100, a specific antagonist of CXCR4, or CXCL12 neutralizing antibody, intrathecally attenuated plantar incision-induced mechanical allodynia and thermal hyperalgesia. Plantar incision also augmented the phosphorylation of NF-κB p65 in spinal cord. Pre intrathecal (i.t.) injection of PDTC, a specific NF-κB activation inhibitor, alleviated plantar incision-induced postsurgical pain and reduced the expression of CXCL12 in spinal cord. Correlated with the upregulation of CXCL12 and CXCR4, plantar incision also resulted in an increased phosphorylation of extracellular signal-regulated kinase 1/2 and Akt in spinal cord. Prior i.t. administration of AMD3100 prevented extracellular signal-regulated kinase, but not Akt, activation in spinal cord. Rats when given a repetitive i.t. PD98059, a specific extracellular signal-regulated kinase inhibitor, started 30 min before surgery also ameliorate plantar incision-induced mechanical and thermal pain hypersensitivity. Conclusion: Our results suggests that plantar incision-induced activation of NF-κB signaling may mediate upregulation of CXCL12 in spinal cord, and CXCL12/CXCR4 signaling via extracellular signal-regulated kinase activation contributes to the genesis of postsurgical pain.
Assuntos
Quimiocina CXCL12/metabolismo , Dor/metabolismo , Receptores CXCR4/metabolismo , Medula Espinal/cirurgia , Animais , Astrócitos/metabolismo , Masculino , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neurônios/metabolismo , Complicações Pós-Operatórias , Ratos Sprague-Dawley , Medula Espinal/metabolismoRESUMO
Abstract: Peripheral nerve injury-caused hyperexcitability and abnormal ectopic discharges in the primary sensory neurons of dorsal root ganglion (DRG) play a key role in neuropathic pain development and maintenance. The two-pore domain background potassium (K2P) channels have been identified as key determinants of the resting membrane potential and neuronal excitability. However, whether K2P channels contribute to neuropathic pain is still elusive. We reported here that K2P1.1, the first identified mammalian K2P channel, was highly expressed in mouse DRG and distributed in small-, medium-, and large-sized DRG neurons. Unilateral lumbar (L) 4 spinal nerve ligation led to a significant and time-dependent reduction of K2P1.1 mRNA and protein in the ipsilateral L4 DRG, but not in the contralateral L4 or ipsilateral L3 DRG. Rescuing this reduction through microinjection of adeno-associated virus-DJ expressing full-length K2P1.1 mRNA into the ipsilateral L4 DRG blocked spinal nerve ligation-induced mechanical, thermal, and cold pain hypersensitivities during the development and maintenance periods. This DRG viral microinjection did not affect acute pain and locomotor function. Our findings suggest that K2P1.1 participates in neuropathic pain development and maintenance and may be a potential target in the management of this disorder.
Assuntos
Gânglios Espinais/metabolismo , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Canais de Potássio/metabolismo , Dor Aguda/metabolismo , Animais , Masculino , Potenciais da Membrana/fisiologia , Camundongos , Neuralgia/fisiopatologia , Neurônios/metabolismo , Traumatismos dos Nervos Periféricos/fisiopatologiaRESUMO
MoHrip1, a protein isolated from Magnaporthe oryzae, belongs to the Alt A 1 (AA1) family. mohrip1 mRNA levels showed inducible expression throughout the infection process in rice. To determine the location of MoHrip1 in M. oryzae, a mohrip1-gfp mutant was generated. Fluorescence microscopy observations and western blotting analysis showed that MoHrip1 was both present in the secretome and abundant in the fungal cell wall. To obtain MoHrip1 protein, we carried out high-yield expression of MoHrip1 in Pichia pastoris. Treatment of tobacco plants with MoHrip1 induced the formation of necrosis, accumulation of reactive oxygen species and expression of several defense-related genes, as well as conferred disease resistance. By fusion to green fluorescent protein, we showed that MoHrip1 was able to bind to the tobacco and rice plant plasma membrane, causing rapid morphological changes at the cellular level, such as cell shrinkage and chloroplast disorganization. These findings indicate that MoHrip1 is a microbe-associated molecular pattern that is perceived by the plant immune system. This is the first study on an AA1 family protein that can bind to the plant plasma membrane.