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BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. METHODS: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. RESULTS: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. CONCLUSION: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.
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Neoplasias del Sistema Nervioso Central , Linfoma no Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Sistema Nervioso Central , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
miRNAs are a family of short, noncoding RNAs that are involved in many processes in melanoma cells. MITF acts as a master regulator of melanocyte function, development and survival by modulating various genes. Hydroxyurea (HU) is used to treat melanoma, and miRNA expression is altered after HU treatment in B16 melanoma cells. In this study, we screened for miRNAs that were upregulated after HU treatment and that targeted the MITF gene. We found that miR-7013-3p exhibited increased expression after HU treatment and could bind to MITF. miR-7013-3p inhibited melanin production, proliferation, and migration and promoted apoptosis in B16 melanoma cells. The results may provide more information on the roles of miR-7013-3p in B16 melanoma cells.
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Hidroxiurea/farmacología , Melanoma/tratamiento farmacológico , MicroARNs/metabolismo , Factor de Transcripción Asociado a Microftalmía/genética , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Regulación de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Hidroxiurea/uso terapéutico , Melaninas/biosíntesis , Melanoma/genética , Melanoma/patología , Ratones , MicroARNs/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: To investigate the value of D-dimer combined with red blood cell distribution width (RDW) in evaluating the disease activity of systemic lupus erythematosus (SLE). METHODS: A total of 105 SLE patients confirmed in our hospital from July 2018 to September 2020 were collected as the SLE group, and 60 healthy persons matched in age and gender during the same period were collected as the control group. According to the SLEDAI score, SLE patients were divided into SLE active group and SLE inactive group, and RDW and D-Dimer levels were detected. RESULTS: The level of RDW in the SLE active group [14.8 (13.4, 16.8)] was significantly higher than that in the SLE inactive group [13.4 (12.6, 14.37)] and control group [12.3 (12, 12.7)], with statistically significant differences (p < 0.05). The D-dimer level in the SLE active group was 1.36 (0.9, 2.25) mg/L, which was significantly higher than that in SLE inactive group [0.34 (0.22, 0.52)] mg/L and control group [0.15 (0.08, 0.19)] mg/L, with statistically significant differences (p < 0.05). Both RDW and D-dimer were positively correlated with the SLEDAI score (r = 0.393, p = 0.000), (r = 0.483, p = 0.000). The results of receiver operating characteristic curve showed that the area under the curve of RDW and D-Dimer alone was 0.875 and 0.954, respectively, while the area under the curve of RDW combined with D-Dimer was the largest, 0.984. CONCLUSIONS: The levels of RDW and D-dimer are closely related to the disease activity of SLE patients, and RDW combined with D-dimer is more valuable in assessing the disease activity of SLE patients.
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Índices de Eritrocitos , Lupus Eritematoso Sistémico , Eritrocitos , Productos de Degradación de Fibrina-Fibrinógeno , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Curva ROCRESUMEN
In recent years, outbreaks of leaf scald have been reported in two chewing cane clones "Guangdong Huangpi" and "Taoshang Guozhe" in Zhejiang province, China. From May to July 2019, we collected 11 and 13 leaf or stalk samples from symptomatic "Guangdong Huangpi" from four farms in Wenling and "Taoshang Guozhe" clones from three farms in Ruian, Zhejiang province, respectively. Leaves in young plants exhibited white pencil-line streaks (Supplement Fig. 1A & 1D) as well as partial or complete chlorosis of the leaf blade (Supplement Fig. 1B & 1E). Internal symptoms included an orange-red discoloration of the vascular bundles at the basal nodes of the stalk and discoloration extension into the internodes (Supplement Fig. 1C & 1F). Leaf and stalk tissues were used for bacterial isolation and purification on XAS medium, which is selective for Xanthomonas albilineans (Davis et al. 1994), using the streak plate method to obtain 24 isolates (Lin et al. 2018). Circular, convex, smooth, shiny and yellow colonies were isolated from all the samples. The pathogenicity of two isolates, XaCN30 from "Guangdong Huangpi" and XaCN43 from "Taoshang Guozhe", was confirmed with Koch's postulates according to the protocol reported by Lin et al. (2018). The incidences of diseased plants (56% and 63%) were observed in individual host clones at 28 d post-inoculation with isolates XaCN30 and XaCN43, respectively. Furthermore, all isolates were confirmed as X. albilineans via molecular methods. PCR amplification was conducted for all 24 isolates using the primer pairs XgyrB1F/XgyrB1R2 (Ntambo et al. 2019) and XAF1/XAR1 (Wang et al. 1999), which targeting the gyrB (encoding the b subunit of the DNA gyrase) and abc (encoding an ABC transporter) genes, and generating 904 bp and 608 bp amplicons, respectively. The PCR fragments were cloned into the pMD19-T vector (TaKaRa, Dalian, China). For each isolate, three single colonies of transformed Escherichia coli DH5α carrying targeted fragment were sequenced. These sequences were deposited into the GenBank with accession no. MT776053-MT776059 and MT776061-MT776077 for gyrB gene and MT776098-MT776104 and MT776106-MT776122 for abc gene. Based on the two concatenated DNA sequences of our 24 isolates, compared with 27 previously reported X. albilineans isolates obtained from the GenBank database, pairwise sequence identity analysis revealed that all 24 isolates from Zhejiang province had 99.4-100% identity with each other, 99.6-100% identity with 14 published domestic isolates, and 98.3-100% identity with 13 foreign isolates. Furthermore, phylogenetic analysis with MEGA 7.0 (Kumar et al. 2016) showed that the isolates from Zhejiang province clustered into two distinct groups (Supplement Fig. 2). One group consisted of 25 Chinese isolates (including all 11 isolates from Wenling) along with four isolates from the French West Indies (GPE PC73, GPE PC17, GPE PC86, and MTQ032), and one isolate from the USA (XaFL07-1), which were assigned to pulsed-field gel electrophoresis (PFGE) group B (Davis et al. 1997; Pieretti et al. 2012). A putative group was also proposed, which included all 13 isolates from Ruian, indicating that isolates from Ruian are distinct from the isolates isolated from other Chinese sugarcane-planting areas, including Wenling. We conclude that leaf scald disease in local clones of chewing cane are caused by X. albilineans in Zhejiang province in China, which will be helpful for leaf scald management in chewing cane, a cash crop.
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Long noncoding RNAs (lncRNAs) are important regulators that have multiple functions in a variety of biological processes. However, the contributions of lncRNAs to follicle-stimulating hormone (FSH) secretion remain largely unknown. In this study, we first identified a novel lncRNA, lncRNA-m433s1, as an intergenic lncRNA located in the cytoplasm. We next used MS2-RIP assays to demonstrate that lncRNA-m433s1 interacted with miR-433. Furthermore, we detected the levels of lncRNA-m433s1, miR-433, and Fshß expression, FSH concentrations, and apoptosis upon overexpression and knockdown of lncRNA-m433s1, revealing that lncRNA-m433s1 upregulated Fshß expression. Globally, lncRNA-m433s1 reduced the inhibitory effect of miR-433 on Fshß and further regulated FSH secretion as a competing endogenous RNA (ceRNA) by sponging miR-433. This ceRNA model will provide novel insight into the regulatory mechanisms of lncRNAs associated with rat reproduction.
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MicroARNs/metabolismo , Adenohipófisis/citología , Animales , Femenino , Hormona Folículo Estimulante de Subunidad beta/genética , Hormona Folículo Estimulante de Subunidad beta/metabolismo , Regulación de la Expresión Génica/fisiología , Masculino , MicroARNs/genética , ARN Largo no Codificante/genética , Ratas , Ratas Sprague-Dawley , Regulación hacia ArribaRESUMEN
Besides their participation in photosynthesis, leaf chloroplasts function in plant responses to stimuli, yet how they direct stimulus-induced stomatal movement remains elusive. Here, we showed that over-reduction of the plastoquinone (PQ) pool by dibromothymoquinone (DBMIB) was closely associated with stomatal closure in plants which required chloroplastic H2O2 generation in the mesophyll. External application of H2 O2 reduced the PQ pool, whereas the cell-permeable reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) reversed the DBMIB-induced over-reduction of the PQ pool and stomatal closure. Mesophyll chloroplasts are key players of extracellular Ca(2+) (Ca(2+)o)-induced stomatal closure, but when treated with either 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU) or NAC they failed to facilitate Ca(2+)o-induced stomatal closure due to the inhibition of chloroplastic H2 O2 synthesis in mesophyll. Similarly, the Arabidopsis electron transfer chain-related mutants npq4-1, stn7 and cas-1 exhibited diverse responses to Ca(2+)o or DBMIB. Transcriptome analysis also demonstrated that the PQ pool signaling pathway shared common responsive genes with the H2 O2 signaling pathway. These results implicated a mechanism for chloroplast-mediated stomatal closure involving the generation of mesophyll chloroplastic H2O2 based on the reduced state of the PQ pool, which is calcium-sensing receptor (CAS) and LHCII phosphorylation dependent.
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Cloroplastos/metabolismo , Hojas de la Planta/metabolismo , Estomas de Plantas/metabolismo , Plantas/metabolismo , Plastoquinona/metabolismo , Peróxido de Hidrógeno/metabolismo , Oxígeno/metabolismo , Plantas/clasificación , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
KEY MESSAGE: Cadmium sensitivity in sultr1;1 - sultr1;2 double mutant with limiting sulfate supply is attributed to the decreased glutathione content that affected oxidative defense but not phytochelatins' synthesis. In plants, glutathione (GSH) homeostasis plays pivotal role in cadmium (Cd) detoxification. GSH is synthesized by sulfur (S) assimilation pathway. Many studies have tried to investigate the role of GSH homeostasis on Cd tolerance using mutants; however, most of them have focused on the last few steps of S assimilation. Until now, mutant evidence that explored the relationship between GSH homeostasis on Cd tolerance and S absorption is rare. To further reveal the role of GSH homeostasis on Cd stress, the wild-type and a sultr1;1-sultr1;2 double mutant which had a defect in two distinct high-affinity sulfate transporters were used in this study. Growth parameters, biochemical or zymological indexes and S assimilation-related genes' expression were compared between the mutant and wild-type Arabidopsis plants. It was found that the mutations of SULTR1;1 and SULTR1;2 did not affect Cd accumulation. Compared to the wild-type, the double mutant was more sensitive to Cd under limited sulfate supply and suffered from stronger oxidative damage. More importantly, under the same condition, lower capacity of S assimilation resulted in decreased GSH content in mutant. Faced to the limited GSH accumulation, mutant seedlings consumed a large majority of GSH in pool for the synthesis of phytochelatins rather than participating in the antioxidative defense. Therefore, homeostasis of GSH, imbalance between antioxidative defense and severe oxidative damage led to hypersensitivity of double mutant to Cd under limited sulfate supply.
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Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Cadmio/farmacología , Glutatión/metabolismo , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Azufre/metabolismoRESUMEN
Hydrogen sulphide (H2S) is emerging as a potential molecule involved in physiological regulation in plants. However, whether H2S regulates iron-shortage responses in plants is largely unknown. Here, the role of H2S in modulating iron availability in maize (Zea mays L. cv Canner) seedlings grown in iron-deficient culture solution is reported. The main results are as follows: Firstly, NaHS, a donor of H2S, completely prevented leaf interveinal chlorosis in maize seedlings grown in iron-deficient culture solution. Secondly, electron micrographs of mesophyll cells from iron-deficient maize seedlings revealed plastids with few photosynthetic lamellae and rudimentary grana. On the contrary, mesophyll chloroplasts appeared completely developed in H2S-treated maize seedlings. Thirdly, H2S treatment increased iron accumulation in maize seedlings by changing the expression levels of iron homeostasis- and sulphur metabolism-related genes. Fourthly, phytosiderophore (PS) accumulation and secretion were enhanced by H2S treatment in seedlings grown in iron-deficient solution. Indeed, the gene expression of ferric-phytosiderophore transporter (ZmYS1) was specifically induced by iron deficiency in maize leaves and roots, whereas their abundance was decreased by NaHS treatment. Lastly, H2S significantly enhanced photosynthesis through promoting the protein expression of ribulose-1,5-bisphosphate carboxylase large subunit (RuBISCO LSU) and phosphoenolpyruvate carboxylase (PEPC) and the expression of genes encoding RuBISCO large subunit (RBCL), small subunit (RBCS), D1 protein (psbA), and PEPC in maize seedlings grown in iron-deficient solution. These results indicate that H2S is closely related to iron uptake, transport, and accumulation, and consequently increases chlorophyll biosynthesis, chloroplast development, and photosynthesis in plants.
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Regulación de la Expresión Génica de las Plantas , Sulfuro de Hidrógeno/metabolismo , Hierro/metabolismo , Proteínas de Plantas/genética , Zea mays/fisiología , Aclimatación , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Deficiencias de Hierro , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/fisiología , Fenómenos Fisiológicos de las Plantas , Proteínas de Plantas/metabolismo , Plantones/crecimiento & desarrollo , Plantones/fisiología , Zea mays/efectos de los fármacos , Zea mays/crecimiento & desarrolloRESUMEN
To assess the neurotoxic effects and redox responses of Aroclor 1254 (A1254) on perinatally exposed rat offspring, A1254 was administered by gavage from gestational day (GD) 6 to postnatal day (PND) 21. Neurobehavioral development, antioxidant enzyme activities, lipid peroxidation (LPO), nitric oxide (NO), and NO synthase (NOS) levels were analyzed in the offspring. Neurobehavioral development analysis revealed delayed appearance of the righting reflex, negative geotaxis, and cliff drop test responses in A1254 exposed group. Developmental A1254 exposure also caused oxidative stress in the brain of PND 22 offspring via reductions in the activity of SOD and GSH-Px, and by promoting a rise in the levels of NO and NOS.
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/toxicidad , Enfermedades del Sistema Nervioso/inducido químicamente , Sistema Nervioso/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Envejecimiento/metabolismo , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/enzimología , Corteza Cerebral/metabolismo , Femenino , Glutatión Peroxidasa/metabolismo , Riñón/efectos de los fármacos , Riñón/enzimología , Riñón/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Ratones , Sistema Nervioso/crecimiento & desarrollo , Sistema Nervioso/metabolismo , Sistema Nervioso/fisiopatología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Embarazo , Distribución Aleatoria , Ratas , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: To explore the mechanism of three kinds extracts (saponins, volatile components, polysaccharide components) of Qingxin Kaiqiao Recipe (QKR) in improving learning and memory capabilities of Alzheimer's disease (AD) rats. METHODS: A controlled comparison method was used. Totally 56 male SD rats were randomly divided into seven groups, i.e., the normal control group, the sham-operation group, the model group, the Aricept group, the saponin group, the benzene group, and the polysaccharide group, 8 in each group. AD rat model was established by bilateral hippocampus injection of Aß1-40 (2 µL, 2.5 µg/µL). The next day after modeling rats in the saponin group, the benzene group, and the polysaccharide group, the saponin group, the Aricept group were intragastrically administered with saponin (at the daily dose of 9 mL/kg, 2.1 g/mL) , benzene (at the daily dose of 3.33 mL/kg, 5.7 g/mL) , polysaccharide (at the daily dose of 8.33 mL/kg, 2.28 g/mL), Aricept (at the daily dose of 1.67 mg/kg), respectively, once a day for 2 consecutive weeks from 10 am every day. Equal volume of normal saline was intragastrically administered to rats in the normal control group and the model group. Learning and memory capabilities were detected using water maze 2 weeks later. Expression levels of synaptotagmin-1 (Syt-1), interleukin-1ß (IL-1ß), glia fibrillary acidic protein (GFAP), and ß-amyloid precursor protein (ßAPP) in the cortex and hippocampus of AD rats were detected using immunohistochemistry. RESULTS: Learning and memory capabilities could be improved by three kinds extracts of QKR. There was no statistical difference in the escape latency between the polysaccharide group and the model group (P >0. 05). The escape lacency was shortened in the rest treatment groups (P < 0.05). The escape latency was obviously prolonged in three kinds extracts of QKR groups, when compared with the Aricept group (P < 0.05, P < 0.01). Compared with the model group, times for crossing platforms were significantly increased in the saponin group and the Aricept group (P < 0.05). Compared with the Aricept group, average times for crossing platforms were significantly lessened in three kinds extracts of QKR groups (P < 0.01). Compared with the sham-operation group, expression levels of Syt-1, IL-1ß, GFAP, and ßAPP in the cortex and hippocampus were increased in the model group (P < 0.01). Compared with the model group, the expression of cortical Syt-1 increased in the saponin group and the benzene group; the expression of cortical IL-1ß increased in the benzene group and the polysaccharide group; the expression of hippocampal GFAP increased in the three kinds extracts of QKR groups; expression levels of Syt-1, IL-1ß, GFAP, and ß-APP in the cortex and hippocampus decreased in the rest treatment groups (all P < 0.05, P < 0.01). Compared with the Aricept group, expression levels of Syt-1, IL-1ß, GFAP, and ßAPP in the cortex and hippocampus were significantly increased in three kinds extracts of QKR groups (P < 0.05, P < 0.01). CONCLUSION: Three kinds extracts of QKR might play roles in anti-AD possibly by decreasing expression levels of Syt-1, IL-1ß, GFAP, and ßAPP in the cortex and hippocampus.
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Enfermedad de Alzheimer , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Aprendizaje/efectos de los fármacos , Precursor de Proteína beta-Amiloide , Animales , Proteína Ácida Fibrilar de la Glía , Hipocampo , Interleucina-1beta , Masculino , Memoria , Ratas , Ratas Sprague-Dawley , SaponinasRESUMEN
OBJECTIVE: To investigate the risk factors for early disseminated intravascular coagulation (DIC) in neonates with sepsis. METHODS: A retrospective clinical study was performed on 100 neonates with a confirmed diagnosis of sepsis between 2012 and 2013. The children were classified into normal coagulation group, non-overt DIC group (early DIC group), and overt DIC group (late DIC group) based on the ISTH overt DIC scoring system. The clinical manifestations and risk factors were analyzed statistically. RESULTS: Early DIC occurred in 44 (44%) cases in the 100 neonates with sepsis. The incidence of sclerema showed significant differences between the three groups (P<0.05). Asphyxia, bleeding, and Gram-negative bacterial infection were independent risk factors for early DIC. CONCLUSIONS: Coagulation function should be actively monitored and early intervention measures should be taken for neonates with asphyxia, bleeding, and Gram-negative bacterial infection to prevent early DIC from progressing to late DIC.
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Coagulación Intravascular Diseminada/etiología , Sepsis/complicaciones , Femenino , Humanos , Recién Nacido , Modelos Logísticos , Masculino , Factores de RiesgoRESUMEN
Production per amount of water used (water use efficiency, WUE) is closely correlated with drought tolerance. Although stomatal aperture can regulate WUE, the underlying molecular mechanisms are still unclear. Previous reports revealed that stomatal closure was inhibited in the calcium-sensing receptor (CAS) antisense line of Arabidopsis (CASas). Here it is shown that decreased drought tolerance and WUE of CASas was associated with higher stomatal conductance due to improper regulation of stomatal aperture, rather than any change of stomatal density. CASas plants also had a lower CO2 assimilation rate that was attributed to a lower photosynthetic electron transport rate, leading to higher chlorophyll fluorescence. Gene co-expression combined with analyses of chlorophyll content and transcription levels of photosynthesis-related genes indicate that CAS is involved in the formation of the photosynthetic electron transport system. These data suggest that CAS regulates transpiration and optimizes photosynthesis by playing important roles in stomatal movement and formation of photosynthetic electron transport, thereby regulating WUE and drought tolerance.
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Proteínas de Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Unión al Calcio/genética , Calcio/metabolismo , Regulación de la Expresión Génica de las Plantas , Agua/fisiología , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Unión al Calcio/metabolismo , Dióxido de Carbono/metabolismo , Clorofila/metabolismo , Deshidratación , Sequías , Transporte de Electrón , Modelos Biológicos , Fotosíntesis/fisiología , Epidermis de la Planta/genética , Epidermis de la Planta/fisiología , Hojas de la Planta/genética , Hojas de la Planta/fisiología , Estomas de Plantas/genética , Estomas de Plantas/fisiología , Transpiración de Plantas/fisiología , Factores de TiempoRESUMEN
Nitric oxide (NO) as a ubiquitous signal molecule plays an important role in plant development and growth. Here, we compared the proteomic changes between NO-overproducing mutant (nox1) and wild-type (WT) of Arabidopsis thaliana using two-dimensional electrophoresis coupled with MALDI-TOF MS. We successfully identified 59 differentially expressed proteins in nox1 mutant, which are predicted to play potential roles in specific cellular processes, such as post-translational modification, energy production and conversion, metabolism, transcription and signal transduction, cell rescue and defense, development and differentiation. Particularly, expression levels of five anti-oxidative enzymes were altered by the mutation; and assays of their respective enzymatic activities indicated an enhanced level of oxidative stress in nox1 mutant. Finally, some important proteins were further confirmed at transcriptional level using quantitative real-time PCR revealing the systemic changes between WT and nox1. The result suggests that obvious morphological changes in the nox1 mutant may be regulated by different mechanisms and factors, while excess endogenous NO maybe one of the possible reasons.
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Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Mutación , Óxido Nítrico/metabolismo , Proteómica/métodos , Antioxidantes/metabolismo , Clorofila/metabolismo , Estrés Oxidativo , Fenotipo , Fotosíntesis , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Transducción de Señal , Transcripción GenéticaRESUMEN
Acid rain (AR), a serious environmental issue, severely affects plant growth and development. As the gymnosperms of conifer woody plants, Pinus massoniana (AR-sensitive) and Taxus wallichiana var. mairei (AR-resistant) are widely distributed in southern China. Under AR stress, significant necrosis and collapsed lesions were found in P. massoniana needles with remarkable yellowing and wilting tips, whereas T. wallichiana var. mairei did not exhibit chlorosis and visible damage. Due to the activation of a large number of stress-related genes and the synthesis of various functional proteins to counteract AR stress, it is important to study the differences in AR-tolerance mechanisms by comparative proteomic analysis of tolerant and sensitive species. This study revealed a total of 65 and 26 differentially expressed proteins that were identified in P. massoniana and T. wallichiana var. mairei, respectively. Among them, proteins involved in metabolism, photosynthesis, signal transduction and transcription were drastically down-regulated in P. massoniana, whereas most of the proteins participating in metabolism, cell structure, photosynthesis and transcription were increased in T. wallichiana var. mairei. These results suggest the distinct patterns of protein expression in the two woody species in response to AR, allowing a deeper understanding of diversity on AR tolerance in forest tree species.
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Lluvia Ácida , Pinus/metabolismo , Proteínas de Plantas/metabolismo , Proteómica/métodos , Taxus/metabolismo , Adaptación Fisiológica , Secuencia de Aminoácidos , Ecosistema , Electroforesis en Gel Bidimensional , Modelos Biológicos , Datos de Secuencia Molecular , Fenotipo , Pinus/anatomía & histología , Pinus/genética , Hojas de la Planta/anatomía & histología , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/clasificación , Proteínas de Plantas/genética , Especificidad de la Especie , Estrés Fisiológico , Taxus/anatomía & histología , Taxus/genéticaRESUMEN
Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 (CFAP300) resulting in a stop codon (p.Glu156 *) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
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Subarachnoid hemorrhage (SAH), a specific subtype of cerebrovascular accident, is characterized by the extravasation of blood into the interstice between the brain and its enveloping delicate tissues. This pathophysiological phenomenon can precipitate an early brain injury (EBI), which is characterized by inflammation and neuronal death. Rutaecarpine (Rut), a flavonoid compound discovered in various plants, has been shown to have protective effects against SAH-induced cerebral insult in rodent models. In our study, we used a rodent SAH model to evaluate the effect of Rut on EBI and investigated the effect of Rut on the inflammatory response and its regulation of SIRT6 expression in vitro. We found that Rut exerts a protective effect on EBI in SAH rats, which is partly due to its ability to inhibit the inflammatory response. Notably, Rut up-regulated Sirtuin 6 (SIRT6) expression, leading to an increase in H3K9 deacetylation and inhibition of nuclear factor-kappa B (NF-[Formula: see text]B) transcriptional activation, thereby mediating the inflammatory response. In addition, further data showed that SIRT6 was proven to mediate the regulation of Rut on the microglial inflammatory response. These findings highlight the importance of SIRT6 in the regulation of inflammation and suggest a potential mechanism for the protective effect of Rut on EBI. In summary, Rut may have the potential to prevent and treat SAH-induced brain injury by interacting with SIRT6. Our findings may provide a new therapeutic strategy for the treatment of SAH-induced EBI.
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Alcaloides Indólicos , FN-kappa B , Quinazolinas , Ratas Sprague-Dawley , Sirtuinas , Hemorragia Subaracnoidea , Animales , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/complicaciones , Sirtuinas/metabolismo , Sirtuinas/genética , Alcaloides Indólicos/farmacología , FN-kappa B/metabolismo , Masculino , Quinazolinas/farmacología , Quinazolinas/uso terapéutico , Modelos Animales de Enfermedad , Lesiones Encefálicas/etiología , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Ratas , Inflamación/tratamiento farmacológico , Inflamación/etiología , Fitoterapia , Transducción de Señal/efectos de los fármacos , Expresión Génica/efectos de los fármacos , QuinazolinonasRESUMEN
Acid rain, as a worldwide environmental issue, can cause serious damage to plants. In this study, we provided the first case study on the systematic responses of arabidopsis (Arabidopsis thaliana (L.) Heynh.) to simulated acid rain (SiAR) by transcriptome approach. Transcriptomic analysis revealed that the expression of a set of genes related to primary metabolisms, including nitrogen, sulfur, amino acid, photosynthesis, and reactive oxygen species metabolism, were altered under SiAR. In addition, transport and signal transduction related pathways, especially calcium-related signaling pathways, were found to play important roles in the response of arabidopsis to SiAR stress. Further, we compared our data set with previously published data sets on arabidopsis transcriptome subjected to various stresses, including wound, salt, light, heavy metal, karrikin, temperature, osmosis, etc. The results showed that many genes were overlapped in several stresses, suggesting that plant response to SiAR is a complex process, which may require the participation of multiple defense-signaling pathways. The results of this study will help us gain further insights into the response mechanisms of plants to acid rain stress.
Asunto(s)
Lluvia Ácida/toxicidad , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Genes de Plantas , ARN de Planta/biosíntesis , Transcriptoma/efectos de los fármacos , Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Perfilación de la Expresión Génica , Redes y Vías Metabólicas/genéticaRESUMEN
Two series of novel AHL analogues were designed, synthesized and evaluated for antibacterial activity under cell membrane conditions in vitro. Analogues 4a-c and 4g-m presented potent activity against Gram-positive bacteria. Especially the analogue 4l exerted the most potent inhibition against Bacillus subtilis with MIC50 value of 1.443µg/ml. To our surprise, analogues 6a-c and 6g showed weak inhibition against Gram-negative bacteria with MIC50 values ranging from 17.589 to 67.840µg/ml. This was the first report about synthesis and antibacterial evaluation in vitro of AHL analogues containing dithioester linkage.
Asunto(s)
4-Butirolactona/análogos & derivados , Antibacterianos/síntesis química , Diseño de Fármacos , 4-Butirolactona/síntesis química , 4-Butirolactona/química , 4-Butirolactona/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Carbamatos/síntesis química , Carbamatos/química , Carbamatos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Percepción de Quorum/efectos de los fármacosRESUMEN
Pb(BO2)2·H2O as sources of B and Pb via a simple hydrothermal process provided the first binodal 5,9-connected lead borate, Pb6B4O11(OH)2 (1). Compound 1 crystallizes in the orthorhombic space group Pnma. The crystal structure is composed of different cluster building units of B4O9 and Pb6O4. Compound 1 has an optical band gap of 3.24 eV.
RESUMEN
OBJECTIVE: To study effects of Qingxin Kaiqiao Recipe (QKR) and its volatile oil on the expressions of Abeta(25-35) glial fibrillary acidic protein (GFAP), beta-amyloid (Abeta), beta-amyloid precursor protein (betaAPP), and Caspase-3 in the cortex and hippocampus of Alzheimer's disease (AD) rats induced by injecting Abeta(25-35) into the bilateral amygdala. METHODS: Totally 32 male SD rats were selected. The AD rat model was establish by injecting Abeta(25-35) from bilateral amygdala. After modeling they were randomly divided into the model group, the Donepezil Hydrochloride group [Donepezil Hydrochloride Tablet (1.67 mg/kg), abbreviated as the DH group], the QKR group (QKR Decoction, 12.67 mL/kg), and the volatile oil group (3.33 mL/kg), 8 rats in each group. Another 8 rats were selected as the normal control group. Equal volume of double distilled water was administered to rats in the normal control group and the model group by gastrogavage, once daily for 2 successive weeks. The Morris water maze test was performed by the end of medication. The escape latency and times of crossing the platform in the water maze test were recorded during the 1st day to the fifth day. The expressions of GFAP, Abeta, betaAPP, and Caspase-3 in the cortex and hippocampus of the rats in each group were detected by immunohistochemical assay. RESULTS: Compared with the model group, the escape latency from the 3rd day to the 5th day was shortened, the expressions of GFAP, Abeta, betaAPP, and Caspase-3 decreased in the cortex and hippocampus, the times of crossing the platform increased in each medication group, showing statistical difference (P < 0.01, P < 0.05). Compared with the DH group, the expressions of Abeta in the cortex and hippocampus decreased, and the betaAPP expression increased in the QKR group. The expressions of GFAP, betaAPP, and Caspase-3 in the cortex and hippocampus increased in the volatile oil group. The escape latency from the 3rd day to the 5th day was obviously prolonged, and the times of crossing the platform decreased in the volatile oil group, showing statistical difference (P < 0.05, P < 0.01). CONCLUSION: QKR could obviously improve the learning and memory capabilities of AD rats, which might be achieved through decreasing the expressions of GFAP, Abeta, betaAPP, and Caspase-3 in the cortex and hippocampus.