RESUMEN
Rhizosphere microbiomes are pivotal for crop fitness, but the principles underlying microbial assembly during root-soil interactions across soils with different nutrient statuses remain elusive. We examined the microbiomes in the rhizosphere and bulk soils of maize plants grown under six long-term (≥ 29 yr) fertilization experiments in three soil types across middle temperate to subtropical zones. The assembly of rhizosphere microbial communities was primarily driven by deterministic processes. Plant selection interacted with soil types and fertilization regimes to shape the structure and function of rhizosphere microbiomes. Predictive functional profiling showed that, to adapt to nutrient-deficient conditions, maize recruited more rhizobacteria involved in nutrient availability from bulk soil, although these functions were performed by different species. Metagenomic analyses confirmed that the number of significantly enriched Kyoto Encyclopedia of Genes and Genomes Orthology functional categories in the rhizosphere microbial community was significantly higher without fertilization than with fertilization. Notably, some key genes involved in carbon, nitrogen, and phosphorus cycling and purine metabolism were dominantly enriched in the rhizosphere soil without fertilizer input. In conclusion, our results show that maize selects microbes at the root-soil interface based on microbial functional traits beneficial to its own performance, rather than selecting particular species.
Asunto(s)
Alphaproteobacteria , Microbiota , Zea mays/microbiología , Microbiología del Suelo , Suelo/química , Rizosfera , FertilizaciónRESUMEN
Rhinoncus sibiricus Faust, a major pest of buckwheat, has invaded the buckwheat cultivation areas of China for years. This pest was first found in Russia in 1940, causing great damage during the entire buckwheat-growing season. In China, there are few records on R. sibiricus, and studies regarding pest damage on buckwheat are unknown. The occurrence and distribution of this species in China is still not clear. We therefore conducted field surveys for 6 yr to identify the distribution range and the degree of pest damage caused by R. sibiricus in the buckwheat-planting areas of China and tested its preference for two Fagopyrum species in common garden experiments. The results showed that R. sibiricus had a larger distribution range in the Northern rather than the Southern part of China, and that pest damage was more serious in northern China. The pest preferred F. tataricum (Tartary buckwheat, Polygonales: Polygonaceae) over F. esculentum (Common buckwheat, Polygonales: Polygonaceae), but caused damage to both, indicating its potential for distribution in southern China. This study clarified the occurrence, distribution, and damage traits of R. sibiricus in the buckwheat cultivation areas of China, which will help explain the pest attack traits and inform strategies for pest control and prediction.
Asunto(s)
Fagopyrum/parasitología , Gorgojos/clasificación , Distribución Animal , Animales , China , Larva , Especificidad de la EspecieRESUMEN
BACKGROUND: The breakdown of the blood-brain barrier (BBB) is intricately linked to the onset and advancement of cognitive impairment and dementia. This investigation explores the correlation between blood-brain barrier permeability, assessed through the cerebrospinal fluid/serum albumin ratio (QAlb), in a clinical cohort and the evolution of cognitive decline. METHODS: This prospective observational cohort study included 295 participants. Cognitive decline progression was characterized by an escalation in the overall deterioration scale and/or clinical dementia rating scores. The investigation delves into the correlation between blood-brain barrier permeability and the advancement of cognitive impairment among patients. RESULTS: The APOE 4 allele and diabetes mellitus among individuals exhibited increased BBB permeability (P < 0.05). Moreover, AD patients exhibited the highest QAlb levels, signifying elevated BBB permeability compared to individuals with MCI and SCD (P < 0.05). After mean 17 months following up, 117 patients (51.31 %) were identified as experiencing cognitive decline progression, and we found that only AD diagnosis, CDR, and QAlb (All P < 0.05) were significant predictors of cognitive decline progression. CONCLUSION: Our study emphasizes the clinical relevance of QAlb in detecting individuals with an elevated risk of cognitive decline. It suggests that heightened BBB permeability could contribute to clinical deterioration and serves as a plausible therapeutic target.
Asunto(s)
Barrera Hematoencefálica , Disfunción Cognitiva , Progresión de la Enfermedad , Humanos , Barrera Hematoencefálica/metabolismo , Masculino , Femenino , Anciano , Estudios Longitudinales , Estudios Prospectivos , Albúmina Sérica/metabolismo , Persona de Mediana Edad , Factores de Riesgo , Permeabilidad , Enfermedad de AlzheimerRESUMEN
The absent in melanoma 2 (AIM2) inflammasome contributes to ischemic brain injury by inducing cell pyroptosis and inflammatory responses. Our research group has previously demonstrated that ATP-sensitive potassium channels (KATP channels) openers can modulate neuronal synaptic plasticity post-ischemic stroke for neuroprotection. However, the specific mechanisms of KATP channels in the inflammatory response following ischemic stroke remain unclear. Here, we assessed cellular damage by observing changes in BV-2 morphology and viability. 2,3,5-Triphenyl tetrazolium chloride (TTC) staining, mNSS scoring, Nissl staining, and TdT-mediated dUTP nick end labeling (TUNEL) staining were used to evaluate behavioral deficits, brain injury severity, and neuronal damage in mice subjected to middle cerebral artery occlusion (MCAO). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were used to measure cell pyroptosis and nuclear factor-kappaB (NF-κB) activation in vivo and in vitro. We observed that AIM2 protein expression was upregulated and localized within the cytoplasm of BV-2 cells. Notably, low-dose Nicorandil treatment reduced inflammatory cytokine secretion and pyroptosis-related protein expression, including AIM2, cleaved cysteinyl aspartate-specific protease-1 (cleaved caspase-1), and Gasdermin D N-terminal (GSDMD-NT). Further investigations revealed that the KATP channel inhibitor 5-HD upregulated p-NF-κB p65, NF-κB p65, and p-IκBα expression, reversing Nicorandil's neuroprotective effect in vivo. In summary, our results suggest that Nicorandil may serve as a potential therapeutic option for ischemic stroke. Targeting AIM2 and NF-κB represents effective strategies for inhibiting neuroinflammation.
Asunto(s)
Accidente Cerebrovascular Isquémico , Canales KATP , Ratones Endogámicos C57BL , FN-kappa B , Enfermedades Neuroinflamatorias , Nicorandil , Animales , Nicorandil/farmacología , Ratones , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/patología , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Masculino , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Canales KATP/metabolismo , Canales KATP/antagonistas & inhibidores , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Transducción de Señal/efectos de los fármacos , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/antagonistas & inhibidores , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patologíaRESUMEN
Potato Fusarium Wilt is a soil-borne fungal disease that can seriously harm potatoes throughout their growth period and occurs at different degrees in major potato-producing areas in China. To reduce the use of chemical agents and improve the effect of biocontrol agents, the inhibitory effects of the fermentation broth of Bacillus subtilis ZWZ-19 (B) and Trichoderma asperellum PT-29 (T) on Fusarium oxysporum were compared under single-culture and co-culture conditions. Furthermore, metabolomic analysis of the fermentation broths was conducted. The results showed that the inhibitory effect of the co-culture fermentation broth with an inoculation ratio of 1:1 (B1T1) was better than that of the separately cultured fermentation broths and had the best control effect in a potted experiment. Using LC-MS analysis, 134 metabolites were determined and classified into different types of amino acids. Furthermore, 10 metabolic pathways had the most significant variations, and 12 were related to amino acid metabolism in the KEGG analysis. A correlation analysis of the 79 differential metabolites generated through the comprehensive comparison between B, T, and B1T1 was conducted, and the results showed that highly abundant amino acids in B1T1 were correlated with amino acids in B, but not in T.
RESUMEN
Crop residue decomposition is an important part of the carbon cycle in agricultural ecosystems, and microorganisms are widely recognized as key drivers during this process. However, we still know little about how nitrogen (N) input and rhizosphere effects from the next planting season impact key straw-decomposing microbial communities. Here, we combined amplicon sequencing and DNA-Stable Isotope Probing (DNA-SIP) to explore these effects through a time-series wheat pot experiment with four treatments: 13C-labeled maize straw addition with or without N application (S1N1 and S1N0), and no straw addition with or without N application (S0N1 and S0N0). The results showed that straw addition significantly reduced soil microbial alpha diversity in the early stages. Straw addition changed microbial beta diversity and increased absolute abundance in all stages. Growing plants in straw-amended soil further reduced bacterial alpha diversity, weakened straw-induced changes in beta diversity, and reduced bacterial and fungal absolute abundance in later stages. In contrast, N application could only increase the absolute abundance of soil bacteria and fungi while having little effect on alpha and beta diversity. The SIP-based taxonomic analysis of key straw-decomposing bacteria further indicated that the dominant phyla were Actinobacteria and Proteobacteria, with overrepresented genera belonging to Vicinamibacteraceae and Streptomyces. Key straw-decomposing fungi were dominated by Ascomycota, with overrepresented genera belonging to Penicillium and Aspergillus. N application significantly increased the absolute abundance of key straw-decomposing microorganisms; however, this increase was reduced by the rhizosphere effect. Overall, our study identified key straw-decomposing microorganisms in straw-amended soil and demonstrated that they exhibited opposite responses to N application and the rhizosphere effect.
RESUMEN
Introduction: Potatoes (Solanum tuberosum L.) can be infected by various viruses, but out of all of viruses, the potato virus Y (PVY) is the most detrimental. Research shows that the potato cultivar YouJin is especially vulnerable to PVY and displays severe symptoms, including leaf vein chlorosis, curled leaf margins, large necrotic spots on the leaf blades, and the growth of small new leaves. Methods: PVY infection in potato cultivar YouJin was confirmed through symptom observation, RT-PCR, and Western blot analysis. Transcriptome sequencing was used to analyze the genes associated with PVY pathogenesis in this cultivar. Result: Transcriptome analysis of differential genes was conducted in this study to examine the pathogenesis of PVY on YouJin. The results showed that 1,949 genes were differentially regulated, including 853 upregulated genes and 1,096 downregulated genes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that carbohydrate synthesis and metabolism pathways were suppressed, and electron transferase and hydrolase activities were reduced. Moreover, there were increased expression levels of protein kinase genes. By focusing on plant-pathogen interaction pathways, six core genes all upregulating the WARK family of transcription factors were obtained. Additionally, a constructed PPI network revealed the identification of key modular differential genes, such as downregulated photosynthesis-related protein genes and upregulated AP2/ERF-ERF transcription factors. Functional network enrichment analysis revealed that PVY infection limited RNA metabolism, glutathionylation, and peroxiredoxin activity while triggering the expression of associated defense genes in YouJin. After analyzing the above, 26 DEGs were screened and 12 DEGs were confirmed via RT-qPCR. Conclusion: These results establish a hypothetical framework for clarifying the pathogenesis of PVY in the YouJin variety of potatoes, which will help design the disease resistance of YouJin.
RESUMEN
Trans-acting small interfering RNAs (tasiRNAs) are 21-nt phased (phased siRNAs) resulting from successive DCL-catalyzed processing from the end of a double-stranded RNA substrate originating from the RDR of an AGO-catalyzed cleaved RNA at a micro RNA target site. Plant tasiRNAs have been synthesized to produce synthetic tasiRNAs (syn-tasiRNAs) targeting viral RNAs that confer viral resistance. In this study, we engineered syn-tasiRNAs to target potato virus Y (PVY) infection by replacing five native siRNAs of TAS1c with 210-bp fragments from the coat protein (CP) region of the PVY genome. The results showed that the transient expression of syn-tasiR-CPpvy2 in Nicotiana benthamiana (N. benthamiana) plants conferred antiviral resistance, supported by the absence of PVY infection symptoms and viral accumulation. This indicated that syn-tasiR-CPpvy2 successfully targeted and silenced the PVY CP gene, effectively inhibiting viral infection. syn-tasiR-CPpvy1 displayed attenuated symptoms and decreased viral accumulation in these plants However, severe symptoms of PVY infection and a similar amount of viral accumulation as the control were observed in plants expressing syn-tasiR-CPpvy3. syn-tasiR-CPpvy/pvx, which targets both PVY and potato virus X (PVX), was engineered using a single precursor. After the transient expression of syn-tasiR-CPpvy/pvx3 and syn-tasiR-CPpvy/pvx5 in N. benthamiana, the plants were resistant to both PVY and PVX. These results suggested that engineered syn-tasiRNAs could not only specifically induce antiviral resistance against one target virus but could also be designed for multi-targeted silencing of different viruses, thereby preventing complex virus infection in plants.
Asunto(s)
Proteínas de la Cápside , Resistencia a la Enfermedad , Nicotiana , Enfermedades de las Plantas , Potyvirus , ARN Interferente Pequeño , Nicotiana/virología , Nicotiana/genética , Nicotiana/inmunología , Proteínas de la Cápside/metabolismo , Proteínas de la Cápside/genética , Potyvirus/fisiología , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/genética , Plantas Modificadas Genéticamente/virologíaRESUMEN
INTRODUCTION: Gastric neuroendocrine carcinoma (GNENs), as a highly malignant gastrointestinal tumor, is characterized by easy postoperative metastasis, and its prognosis has always been poor compared to other gastrointestinal tumors. Due to its rarity, there have been few case reports and studies on it. As of now, there is no clear diagnosis and treatment sequence and guidelines. In this report, we present a case of GNENs that underwent first-line treatment after surgery. The patient achieved an excellent prognosis and survival after a combination of chemotherapy resistance and immunotherapy. This report aims to provide valuable reference and guidance for the treatment of GNENs in the future. Therefore, we conducted a literature review on GNENs. PATIENT CONCERNS: A 61-year-old man was admitted to the hospital with complaints of upper abdominal distension and discomfort that had been persistent for 1 month. During the endoscopy examination, a 2.5 cm irregular deep mucosal defect was observed at the center of the gastric angle. The defect appeared covered with dirty moss, had a hard texture, and exhibited a tendency to bleed upon contact. DIAGNOSIS: Biopsy results confirmed the presence of a medium to poorly differentiated adenocarcinoma in the gastric horn. Subsequently, the patient underwent surgery, and the removed specimen was diagnosed as GNENs. INTERVENTION: Postoperative chemotherapy combined with immunotherapy. OUTCOME: The patient in this case achieved a good prognosis and extremely long survival [overall survivalâ >â 3 years+] after receiving first-line treatment, which included chemotherapy, drug resistance and immunotherapy, and is currently in good health condition. The tumor is not sensitive to the standard EP regimen for neuroendocrine carcinoma, but after being replaced with oxaliplatin based regimen combined with immunotherapy, partial response was obtained, indicating a synergistic effect between chemotherapy and immunity. After treatment, it remained stable for a considerable period of time. CONCLUSION: Immunotherapy, as a new mode of cancer treatment can provide new guidance and ideas for the treatment of GNENs.
Asunto(s)
Adenocarcinoma , Carcinoma Neuroendocrino , Neoplasias Gástricas , Masculino , Humanos , Persona de Mediana Edad , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/patología , Adenocarcinoma/patología , Pronóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , InmunoterapiaRESUMEN
Potato (Solanum tuberosum L.) is an important vegetable crop that plays a pivotal role in the world, especially given its potential to feed the world population and to act as the major staple food in many developing countries. Every year, significant crop loss is caused by viral diseases due to a lack of effective agrochemical treatments, since only transmission by insect vectors can be combated with the use of insecticides, and this has been an important factor hindering potato production. With the rapid development of molecular biology and plant genetic engineering technology, transgenic approaches and non-transgenic techniques (RNA interference and CRISPR-cas9) have been effectively employed to improve potato protection against devastating viruses. Moreover, the availability of viral sequences, potato genome sequences, and host immune mechanisms has remarkably facilitated potato genetic engineering. In this study, we summarize the progress of antiviral strategies applied in potato through engineering either virus-derived or plant-derived genes. These recent molecular insights into engineering approaches provide the necessary framework to develop viral resistance in potato in order to provide durable and broad-spectrum protection against important viral diseases of solanaceous crops.
RESUMEN
Allelopathic interactions between plants serve as powerful tools for weed control. Despite the increasing understanding of the allelopathic mechanisms between different plant species, the inhibitory effects of B. oleracea on weed growth remain poorly understood. In this study, we conducted experiments to demonstrate that B. oleracea extract can suppress the germination of Panicum miliaceum L.varruderale Kit. seeds as well as of the roots, shoots and hypocotyl elongation of P. miliaceum seedlings. Furthermore, we observed that B. oleracea extract reduced the levels of hydrogen peroxide and superoxide anion in the roots while increasing the activities of catalase and ascorbate peroxidase. In the shoots, B. oleracea extract enhanced the activities of superoxide dismutase and peroxidase. Moreover, the use of the extract led to an increase in the content of phytohormones (indole-3-acetic acid, indole-3-acetaldehyde, methyl indole-3-acetate, N6-isoPentenyladenosine, dihydrozeatin-7-glucoside, abscisic acid and abscisic acid glucose ester) in P. miliaceum seedlings. Interestingly, the aqueous extract contained auxins and their analogs, which inhibited the germination and growth of P. miliaceum. This may contribute to the mechanism of the B. oleracea-extract-induced suppression of P. miliaceum growth.
RESUMEN
Synaptogenesis is considered necessary for learning and memory. Recently, it has been suggested that progesterone (PROG) effects synaptogenesis of the cerebellar Purkinje cell, helps alleviate symptoms of multiple sclerosis and helps arrest spinal cord neurodegeneration. However, it is unclear whether PROG influences synaptic plasticity in central nervous system neurons after global cerebral ischemia. The purpose of the present study was to reveal PROG's influence on postischemic synaptogenesis in the CA1 region of the hippocampus in rats. Global cerebral ischemia was induced in male Sprague-Dawley rats by the 4-vessel occlusion (4-VO) method. To determine the amount of synaptogenesis, growth-associated protein 43 (GAP-43) and synaptophysin (SYP) expression were examined by immunohistochemical, reverse transcription-polymerase chain reaction (RT-PCR) and western blot techniques. Histological and behavioral tests were used to indicate the effect of PROG on global cerebral ischemia. Recovery times were 3, 7, 14, 21, and 35 days after surgery. We found that PROG increased the expression of GAP-43 and SYP. In addition, there was a significant increase in neuronal cell density and improvement ability to remain on an accelerating rotarod observed in the 4-VO rats treated with PROG compared to vehicle. We propose that PROG helped enable synaptogenesis in the CA1 region of therat hippocampus after global cerebral ischemia in rats.
Asunto(s)
Isquemia Encefálica/patología , Región CA1 Hipocampal/fisiopatología , Neurogénesis/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Progesterona/farmacología , Sinapsis/efectos de los fármacos , Animales , Región CA1 Hipocampal/efectos de los fármacos , Recuento de Células/métodos , Modelos Animales de Enfermedad , Proteína GAP-43/genética , Proteína GAP-43/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Prueba de Desempeño de Rotación con Aceleración Constante , Sinaptofisina/genética , Sinaptofisina/metabolismo , Factores de TiempoRESUMEN
With population growth and aging, more and more patients with cerebral infarction have varying degrees of disability. ATP-sensitive potassium (KATP) channels regulate many cellular functions by coupling metabolic status with cell membrane electrical activity. Nicorandil (N-(2-hydroxyethyl)-nicotinamide nitrate) is the first KATP channel opener approved for clinical use. It has been reported that it might exert protective effects on the cerebral infarction by increasing cerebral blood flow and reducing inflammation. However, only a few studies explored its role in synaptogenesis. We made the rat model of middle cerebral artery occlusion (MCAO). Nicorandil was administered to rats via oral administration immediately after the surgery at a dose of 7.5 mg/kg and then daily for the next days. Infarct volume, cerebral edema, neurological deficits, cognitive impairment, and the level of Synaptophysin (SYP)ãGrowth associated protein-43 (GAP43) and neuronal nuclear antigen (NeuN) levels were measured to evaluate the effect of nicorandil. Our data showed that nicorandil treatment could decrease brain damage, improve learning and memory, and increase SYPãGAP43 and NeuN level. Taken together, we propose that nicorandil, as an opener of the KATP channel, provides a neuroprotective role in MCAO by promoting synaptic connections.
Asunto(s)
Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Canales KATP/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Nicorandil/uso terapéutico , Sinapsis/efectos de los fármacos , Vasodilatadores/uso terapéutico , Animales , Circulación Cerebrovascular/efectos de los fármacos , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Fármacos Neuroprotectores/farmacología , Nicorandil/farmacología , Ratas , Ratas Sprague-Dawley , Sinapsis/metabolismo , Sinapsis/patología , Vasodilatadores/farmacologíaRESUMEN
Caudal paramedian midbrain infarction (CPMI) is an extremely rare form of ischemic stroke and related clinical studies are scarce. Our aim is to investigate the clinical features, neuroradiological findings and stroke etiology of CPMI. We conducted a retrospective study of 12 patients with CPMI, confirmed by diffusion-weighted MRI from 6820 cerebral infarction patients at our stroke center from January 2012 to August 2018. Experienced neurologists evaluated the clinical manifestations, neuroimaging findings and stroke mechanisms. Twelve patients (11 men, 1 woman) aged 42-81 years old met the study inclusion criteria. Seven patients had a unilateral infarction (two right-sided, five left-sided) and five had bilateral infarctions. Sagittal image showed a backward oblique sign in the lower level of the midbrain. Significantly, the bilateral CPMIs presented with a characteristic "V-shaped" appearance in the axial MRI. All patients presented with bilateral cerebellar dysfunction which included dysarthric speech, truncal or gait ataxia and four-limb ataxia. In addition, diplopia and internuclear ophthalmoplegia were frequently encountered in CPMI. Five (41.7%) patients were classified with large artery atherosclerosis, four (33.3%) with small vessel disease, two (16.7%) with cardiogenic embolism, and one (8.3%) with undetermined etiology. CPMI is a rare cerebrovascular disease that destroys the Wernekink commissure, medial longitudinal fasciculi and other adjacent structures. It is characterized by bilateral cerebellar ataxia and eye movement disorders, mainly internuclear ophthalmoplegia. A distinct "V-shaped" radiological feature can be seen in bilateral CPMI patients. The primary mechanisms of unilateral CPMI involve small vessel disease. The underlying stroke mechanisms of bilateral CPMI are either large artery atherosclerosis disease or cardiac embolism.
Asunto(s)
Ataxia Cerebelosa/diagnóstico por imagen , Infarto Cerebral/diagnóstico por imagen , Mesencéfalo/diagnóstico por imagen , Trastornos de la Motilidad Ocular/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Ataxia Cerebelosa/etiología , Infarto Cerebral/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Motilidad Ocular/etiología , Estudios Retrospectivos , Accidente Cerebrovascular/complicacionesRESUMEN
BACKGROUND AND PURPOSE: Inflammation and ferroptosis in astrocytes can be induced by external injuries, which results in excessive production of inflammatory factors and further injury on neurons. Alleviating ferroptosis might be an effective way to protect the brain from external injuries. The present study aims to explore the protective effects of Ferrostatin-1 against ferroptosis induced by Angiotensin II and the underlying mechanism. METHODS: The mouse primary astrocytes were isolated from the cortices of mice. The astrocytes were stimulated using 10 µM angiotensin II in the presence or absence of 1 or 2 µM Ferrostatin-1. The gene expression levels of AT1R, IL-6, IL-1ß, COX-2, GFAP, and GPx4 were evaluated using qRT-PCR. Western Blot was used to determine the protein levels of AT1R, COX-2, GFAP, GPx4, Nrf2, and HO-1 and ELISA was used to detect the concentrations of IL-6, IL-1ß, and PGE2. The ROS levels were evaluated using DHE staining and the reduced GSH level was determined using GSH detection kits. RESULTS: The expression levels of AT1R, IL-6, IL-1ß, COX-2, and GFAP in the astrocytes were significantly elevated by stimulation with Ang II and greatly suppressed by the introduction of Ferrostatin-1 in a dose-dependent manner. The promoted ROS level and inhibited GSH level in the astrocytes by the stimulation with Ang II were significantly reversed by Ferrostatin-1. Down-regulated GPx4, Nrf2, and HO-1 in the astrocytes induced by Ang II were extremely up-regulated by the treatment of Ferrostatin-1 in a dose-dependent manner. CONCLUSION: Ferrostatin-1 alleviates angiotensin II (Ang II)- induced inflammation and ferroptosis by suppressing the ROS levels and activating the Nrf2/HO-1 signaling pathway.
Asunto(s)
Angiotensina II/toxicidad , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Astrocitos/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Ciclohexilaminas/farmacología , Ferroptosis/efectos de los fármacos , Inflamación/prevención & control , Fenilendiaminas/farmacología , Animales , Astrocitos/metabolismo , Astrocitos/patología , Células Cultivadas , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Citocinas/metabolismo , Hemo-Oxigenasa 1/metabolismo , Inflamación/metabolismo , Inflamación/patología , Mediadores de Inflamación/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
The antibiotic 2,4-diacetylphoroglucinol (2,4-DAPG), produced by the Gram-negative rod-shaped bacterium Pseudomonas fluorescens 2P24, is active against various soil-borne bacterial and fungal pathogens that cause plant diseases. Biosynthesis of 2,4-DAPG is controlled by regulating expression of the phlACBD operon at the post-transcriptional level. The phlG gene is located between the phlF and phlH genes, upstream of the phlACBD biosynthetic operon. Herein, we cloned the phlG gene, generated a phlG deletion mutant, and investigated its regulatory role in 2,4-DAPG biosynthesis. The results showed that deletion of phlG had no effect on the biosynthesis of 2,4-DAPG, but it affected conversion of 2,4-DAPG to its precursor monoacetylphloroglucinol (MAPG). The global regulatory factor encoded by gacS positively regulated expression of phlG, while rsmE negatively regulated its expression. Deleting phlG did not alter the ability of the bacterium to colonise plants or promote plant growth. These results suggest that phlG collaborates with other factors to regulate production of the antibiotic 2,4-DAPG in P. fluorescens 2P24.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Floroglucinol/análogos & derivados , Enfermedades de las Plantas/inmunología , Pseudomonas fluorescens/crecimiento & desarrollo , Triticum/crecimiento & desarrollo , Proteínas Bacterianas/genética , Floroglucinol/metabolismo , Enfermedades de las Plantas/microbiología , Pseudomonas fluorescens/metabolismo , Triticum/efectos de los fármacos , Triticum/microbiologíaRESUMEN
Growth/differentiation factor-5 (GDF-5), a member of the transforming growth factor-beta (TGF-ß) superfamily, has been shown to protect rat dopaminergic neurons against insult both in embryonic neuronal culture and in Parkinson's disease models. However, whether GDF-5 exerts neuroprotective effects in hippocampal neurons is unclear. Here, we show that both mRNA levels and protein levels of GDF-5 are decreased in the mouse hippocampus upon kainic acid (KA) treatment. KA induced dramatic neuronal loss specifically in the cornu ammonis 1 (CA1) and CA3 areas of the mouse hippocampus, while intracerebral infusion of GDF-5 prevented this neuronal loss. The neuroprotective effects of GDF-5 were recapitulated by constitutively active bone morphogenetic protein type IB receptor (BMPRIB-CA) and could be blocked by BMPRI kinase inhibitor LDN-193189. Furthermore, the neuroprotective effects of GDF-5 were mediated through the prevention of apoptosis, which was indicated by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and reduced cleaved caspase 3 expression level. Thus, we conclude that GDF-5 protects hippocampal neurons against KA-induced neurodegeneration by signaling through BMPRIB, suggesting a therapeutic potential for GDF-5 in neurodegenerative diseases.
Asunto(s)
Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/metabolismo , Factor 5 de Diferenciación de Crecimiento/administración & dosificación , Factor 5 de Diferenciación de Crecimiento/metabolismo , Hipocampo/efectos de los fármacos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Ácido Kaínico/administración & dosificación , Ratones , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedades Neurodegenerativas/metabolismo , Neuronas/metabolismo , Neuronas/patología , ARN Mensajero/metabolismo , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Ischemic edema can alter the structure and permeability of the blood-brain barrier. Recent studies have reported that progesterone reduces cerebral edema after cerebral ischemia. However, the underlying mechanism of this effect has not yet been elucidated. In the present study, progesterone effectively reduced Evans blue extravasation in the ischemic penumbra, but not in the ischemic core, 48 hours after cerebral ischemia in rats. Progesterone also inhibited the down-regulation of gene and protein levels of occludin and zonula occludens-1 in the penumbra. These results indicate that progesterone may effectively inhibit the down-regulation of tight junctions, thereby maintaining the integrity of the blood-brain barrier and reducing cerebral edema.
RESUMEN
Cervical dumbbell tumor poses great difficulties for neurosurgical treatment and incurs remarkable local recurrence rate as the formidable problem for neurosurgery. However, as the routine preoperative evaluation scheme, MRI and CT failed to reveal the mutual three-dimensional relationships between tumor and adjacent structures. Here, we report the clinical application of MSCTA and VRT in three-dimensional reconstruction of cervical dumbbell tumors. From January 2012 to July 2014, 24 patients diagnosed with cervical dumbbell tumor were retrospectively analyzed. All patients enrolled were indicated for preoperative MSCTA/VRT image reconstruction to explore the three-dimensional stereoscopic anatomical relationships among neuroma, spinal cord and vertebral artery to achieve optimal surgical approach from multiple configurations and surgical practice. Three-dimensional mutual anatomical relationships among tumor, adjacent vessels and vertebrae were vividly reconstructed by MSCTA/VRT in all patients in accordance with intraoperative findings. Multiple configurations for optimal surgical approach contribute to total resection of tumor, minimal damage to vessels and nerves, and maximal maintenance of cervical spine stability. Preoperative MSCTA/VRT contributes to reconstruction of three-dimensional stereoscopic anatomical relationships between cervical dumbbell tumor and adjacent structures for optimal surgical approach by multiple configurations and reduction of intraoperative damages and postoperative complications.
RESUMEN
OBJECTIVE: To detect the effects of 17ß-estradiol (E2) on the expression of calbindin-D9k (CaBP-9k) in pituitary GH3 cells, and to determine the antagonistic effect of a selective estrogen receptor (ER) antagonist (ICI 182 780) on CaBP-9k expression. METHODS: A rat pituitary prolactinoma cell line (GH3 cells) was used in an in vitro model. The localization of CaBP-9k in GH3 cells was observed by immunofluorescence. GH3 cells were cultured with the addition of E2 medium for 24 hours. The levels of CaBP-9k mRNA and protein expression in different groups were analyzed by RT-PCR and Western blot analysis. The ER antagonist, ICI 182 780, was added to GH3 cells before E2 (10(-8) M) at a concentration of 10(-6) M to investigate the regulation of an ER-mediated pathway on CaBP-9k expression. RESULTS: E2 had a stimulatory effect on CaBP-9k expression of GH3 cells in a dose-dependent manner; the level of CaBP-9k expression was higher when treated with a higher concentration of E2. ICI 182 780 suppressed the stimulatory effect of E2 on CaBP-9k expression in GH3 cells. The level of CaBP-9k expression was significantly reduced by co-administration of E2 with ICI 182 780 in GH3 cells. The immunoprecipitation results confirmed that CaBP-9k interacts directly with ERα, and E2 increases the interaction between CaBP-9k and ERα. CONCLUSION: Estrogen induces CaBP-9k expression via an ERα-mediated pathway and CaBP-9k directly combines with ERα, suggesting that CaBP-9k is involved in the biological effects mediated by an ER pathway in GH3 cells.