RESUMO
The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.
Assuntos
Pontos de Checagem da Fase M do Ciclo Celular , Meiose , Animais , Feminino , Camundongos , Ciclossomo-Complexo Promotor de Anáfase/genética , Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Oócitos/metabolismo , Ubiquitinas/metabolismoRESUMO
Arabidopsis RESISTANCE TO POWDERY MILDEW 8.1 (RPW8.1) is an important tool for engineering broad-spectrum disease resistance against multiple pathogens. Ectopic expression of RPW8.1 leads to enhanced disease resistance with cell death at leaves and compromised plant growth, implying a regulatory mechanism balancing RPW8.1-mediated resistance and growth. Here, we show that RPW8.1 constitutively enhances the expression of transcription factor WRKY51 and activates salicylic acid and ethylene signalling pathways; WRKY51 in turn suppresses RPW8.1 expression, forming a feedback regulation loop. RPW8.1 and WRKY51 are both induced by pathogen infection and pathogen-/microbe-associated molecular patterns. In ectopic expression of RPW8.1 background (R1Y4), overexpression of WRKY51 not only rescues the growth suppression and cell death caused by RPW8.1, but also suppresses RPW8.1-mediated broad-spectrum disease resistance and pattern-triggered immunity. Mechanistically, WRKY51 directly binds to and represses RPW8.1 promoter, thus limiting the expression amplitude of RPW8.1. Moreover, WRKY6, WRKY28 and WRKY41 play a role redundant to WRKY51 in the suppression of RPW8.1 expression and are constitutively upregulated in R1Y4 plants with WRKY51 being knocked out (wrky51 R1Y4) plants. Notably, WRKY51 has no significant effects on disease resistance or plant growth in wild type without RPW8.1, indicating a specific role in RPW8.1-mediated disease resistance. Altogether, our results reveal a regulatory circuit controlling the accumulation of RPW8.1 to an appropriate level to precisely balance growth and disease resistance during pathogen invasion.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Resistência à Doença/genética , Retroalimentação , Arabidopsis/metabolismo , Morte Celular , Doenças das Plantas/genética , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
Neijiang (NJ) and Yacha (YC) are two indigenous pig breeds in the Sichuan basin of China, displaying higher resistance to diseases, lower lean ratio, and slower growth rate than the commercial Western pig breed Yorkshire (YS). The molecular mechanisms underlying the differences in growth and development between these pig breeds are still unknown. In the present study, five pigs from NJ, YC, and YS breeds were subjected to the whole genome resequencing, and then the differential single-nucleotide polymorphisms (SNPs) were screened using a 10-kb window sliding in 1-kb step using the Fst method. Finally, 48,924, 48,543, and 46,228 nonsynonymous single-nucleotide polymorphism loci (nsSNPs) were identified between NJ and YS, NJ and YC, and YC and YS, which highly or moderately affected 2,490, 800, and 444 genes, respectively. Moreover, three nsSNPs were detected in the genes of acetyl-CoA acetyltransferase 1 (ACAT1) insulin-like growth factor 2 receptor (IGF2R), insulin-like growth factor 2 and mRNA-binding protein 3 (IGF2BP3), which potentially affected the transformation of acetyl-CoA to acetoacetyl-CoA and the normal functions of the insulin signaling pathways. Moreover, serous determinations revealed significantly lower acetyl-CoA content in YC than in YS, supporting that ACAT1 might be a reason explaining the differences in growth and development between YC and YS breeds. Contents of phosphatidylcholine (PC) and phosphatidic acid (PA) significantly differed between the pig breeds, suggesting that glycerophospholipid metabolism might be another reason for the differences between Chinese and Western pig breeds. Overall, these results might contribute basic information to understand the genetic differences determining the phenotypical traits in pigs.
Assuntos
Suínos , Animais , Acetilcoenzima A , Genoma , Polimorfismo de Nucleotídeo Único , Suínos/genética , Suínos/crescimento & desenvolvimentoRESUMO
Many rice microRNAs have been identified as fine-tuning factors in the regulation of agronomic traits and immunity. Among them, Osa-miR535 targets SQUAMOSA promoter binding protein-like 14 (OsSPL14) to positively regulate tillers but negatively regulate yield and immunity. Here, we uncovered that Osa-miR535 targets another SPL gene, OsSPL4, to suppress rice immunity against Magnaporthe oryzae. Overexpression of Osa-miR535 significantly decreased the accumulation of the fusion protein SPL4TBS -YFP that contains the target site of Osa-miR535 in OsSPL4. Consistently, Osa-miR535 mediated the cleavage of OsSPL4 mRNA between the 10th and 11th base pair of the predicted binding site at the 3' untranslated region. Transgenic rice lines overexpressing OsSPL4 (OXSPL4) displayed enhanced blast disease resistance accompanied by enhanced immune responses, including increased expression of defense-relative genes and up-accumulated H2 O2 . By contrast, the knockout mutant osspl4 exhibited susceptibility. Moreover, OsSPL4 binds to the promoter of GH3.2, an indole-3-acetic acid-amido synthetase, and promotes its expression. Together, these data indicate that Os-miR535 targets OsSPL4 and OsSPL4-GH3.2, which may parallel the OsSPL14-WRKY45 module in rice blast disease resistance.
Assuntos
Magnaporthe , Oryza , Proteínas de Transporte/metabolismo , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Magnaporthe/metabolismo , Oryza/metabolismo , Doenças das Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Arabidopsis RESISTANCE TO POWDERY MILDEW 8.2 (RPW8.2) is specifically induced by the powdery mildew (PM) fungus (Golovinomyces cichoracearum) in the infected epidermal cells to activate immunity. However, the mechanism of RPW8.2-induction is not well understood. Here, we identify a G. cichoracearum effector that interacts with RPW8.2, named Gc-RPW8.2 interacting protein 1 (GcR8IP1), by a yeast two-hybrid screen of an Arabidopsis cDNA library. GcR8IP1 is physically associated with RPW8.2 with its REALLY INTERESTING NEW GENE finger domain that is essential and sufficient for the association. GcR8IP1 was secreted and translocated into the nucleus of host cell infected with PM. Association of GcR8IP1 with RPW8.2 led to an increase in RPW8.2 in the nucleus. In turn, the nucleus-localized RPW8.2 promoted the activity of the RPW8.2 promoter, resulting in transcriptional self-amplification of RPW8.2 to boost immunity at infection sites. Additionally, ectopic expression or host-induced gene silencing of GcR8IP1 supported its role as a virulence factor in PM. Altogether, our results reveal a mechanism of RPW8.2-dependent defense strengthening via altered partitioning of RPW8.2 and transcriptional self-amplification triggered by a PM fungal effector, which exemplifies an atypical form of effector-triggered immunity.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ascomicetos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Resistência à Doença , Ascomicetos/fisiologia , Doenças das Plantas/microbiologiaRESUMO
Background: As an emerging arrhythmia monitor, ambulatory smartwatch electrocardiogram (ECG) provides an option for home-based monitoring of delayed new-onset arrhythmic events after transcatheter aortic valve replacement (TAVR). We aimed to validate the diagnostic efficacy of a consumer smartwatch ECG in TAVR recipients, while further explore the occurrence rate of both tachy- and brady-arrhythmia for 30 days after discharge to support risk management. Methods: Consecutive TAVR recipients from February 26th, 2021 to December 13th, 2021 were enrolled prospectively, receiving simultaneous 24-hour Holter and 12-lead ECG compared with smartwatch ECG during hospitalization and daily smartwatch ECG collection for 30 days after discharge. Results: Among 110 patients, the efficacy of smartwatch ECG presented sensitivity and specificity in diagnosing atrial fibrillation (AF) as 1.00 and 0.97, left bundle branch block (LBBB) as 0.61 and 0.88, and right bundle branch block (RBBB) as 0.60 and 0.97, respectively, compared with 24-hour Holter; presented sensitivity and specificity in diagnosing AF as 0.88 and 1.00, LBBB as 0.90 and 0.96, and RBBB as 0.83 and 0.94, respectively, compared with 12-lead ECG. At 30-day follow-up, new-onset arrhythmia included new-onset severe conduction disturbance (SCD) (23.6%), new-onset AF (21.8%), new-onset permanent LBBB (14.5%) and new-onset permanent RBBB (0.9%); 69.2% (36/52) of early new-onset LBBB recovered at 30-day follow-up. Conclusions: The diagnostic efficacy of consumer smartwatch ECG in arrhythmic events among TAVR population was acceptable, which provided a recommendable option for home-based management. Clinical Trial Registration: "Continuously ambulatory rhythm monitoring and predictors of electrocardio-related adverse events in 30 days after transcatheter aortic valve replacement"; Identifier: ChiCTR2000041244; http://www.chictr.org.cn/showproj.aspx?proj=66324.
RESUMO
MicroRNAs (miRNAs) play vital roles in plant development and defence responses against various stresses. Here, we show that blocking miR1871 improves rice resistance against Magnaporthe oryzae and enhances grain yield simultaneously. The transgenic lines overexpressing miR1871 (OX1871) exhibit compromised resistance, suppressed defence responses and reduced panicle number resulting in slightly decreased yield. In contrast, the transgenic lines blocking miR1871 (MIM1871) show improved resistance, enhanced defence responses and significantly increased panicle number leading to enhanced yield per plant. The RNA-seq assay and defence response assays reveal that blocking miR1871 resulted in the enhancement of PAMP-triggered immunity (PTI). Intriguingly, miR1871 suppresses the expression of LOC_Os06g22850, which encodes a microfibrillar-associated protein (MFAP1) locating nearby the cell wall and positively regulating PTI responses. The mutants of MFAP1 resemble the phenotype of OX1871. Conversely, the transgenic lines overexpressing MFAP1 (OXMFAP1) or overexpressing both MFAP1 and miR1871 (OXMFAP1/OX1871) resemble the resistance of MIM1871. The time-course experiment data reveal that the expression of miR1871 and MFAP1 in rice leaves, panicles and basal internode is dynamic during the whole growth period to manipulate the resistance and yield traits. Our results suggest that miR1871 regulates rice yield and immunity via MFAP1, and the miR8171-MFAP1 module could be used in rice breeding to improve both immunity and yield.
Assuntos
Magnaporthe , Oryza , Ascomicetos , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas/genética , Magnaporthe/fisiologia , Oryza/metabolismo , Melhoramento Vegetal , Doenças das Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Rice production is threatened by multiple pathogens. Breeding cultivars with broad-spectrum disease resistance is necessary to maintain and improve crop production. Previously we found that overexpression of miR160a enhanced rice blast disease resistance. However, it is unclear whether miR160a also regulates resistance against other pathogens, and what the downstream signaling pathways are. Here, we demonstrate that miR160a positively regulates broad-spectrum resistance against the causative agents of blast, leaf blight and sheath blight in rice. Mutations of miR160a-targeted Auxin Response Factors result in different alteration of resistance conferred by miR160a. miR160a enhances disease resistance partially by suppressing ARF8, as mutation of ARF8 in MIM160 background partially restores the compromised resistance resulting from MIM160. ARF8 protein binds directly to the promoter and suppresses the expression of WRKY45, which acts as a positive regulator of rice immunity. Mutation of WRKY45 compromises the enhanced blast resistance and bacterial leaf blight resistance conferred by arf8 mutant. Overall, our results reveal that a microRNA coordinates rice broad-spectrum disease resistance by suppressing multiple target genes that play different roles in disease resistance, and uncover a new regulatory pathway mediated by the miR160a-ARF8 module. These findings provide new resources to potentially improve disease resistance for breeding in rice.
Assuntos
Magnaporthe , Oryza , Resistência à Doença/genética , Magnaporthe/metabolismo , Oryza/metabolismo , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Melhoramento VegetalRESUMO
In order to study the structure-activity relationship (SAR) of C21-steroidal glycosides toward human cancer cell lines and explore more potential anticancer agents, a series of 3ß-O-neoglycosides of caudatin and its analogues were synthesized. The results revealed that most of peracetylated 3ß-O-monoglycosides demonstrated moderate to significant antiproliferative activities against four human cancer cell lines (MCF-7, HCT-116, HeLa, and HepG2). Among them, 3ß-O-(2,3,4-tri-O-acetyl-ß-L-glucopyranosyl)-caudatin (2k) exhibited the highest antiproliferative activity aganist HepG2 cells with an IC50 value of 3.11 µM. Mechanical studies showed that compound 2k induced both apoptosis and cell cycle arrest at S phase in a dose dependent manner. Overall, these present findings suggested that glycosylation is a promising scaffold to improve anticancer activity for naturally occurring C21-steroidal aglycones, and compound 2k represents a potential anticancer agent deserved further investigation.
Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
A series of novel D-ring fused or substituted steroidal N-heterocycles were synthesized, and their chemical structures were characterized by spectroscopic analysis. The anticancer activity of these compounds against four human cancer cell lines (MCF-7, H1299, HeLa and HepG2) were evaluated and the structure-activity relationship (SAR) was also investigated. Compound 3c displayed significant inhibitory activity on the four cancer cells with IC50 values ranging from 3.88 to 10.05â µM. Overall, these studies indicated that construction of N-heterocyclic system with D-ring substituted containing a double bond at C-16 and C-17 or D-ring fused with [17,16-d]azolo[1,5-a]pyrimidine could be a promising strategy to improve antitumor activity for steroids deserved further investigation.
Assuntos
Antineoplásicos , Humanos , Antineoplásicos/química , Pirimidinas/química , Esteroides/farmacologia , Esteroides/química , Relação Estrutura-Atividade , Células HeLa , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Proliferação de Células , Linhagem Celular TumoralRESUMO
In recent years, the MYB-related gene family has been found pivotal in plant growth and development. MYB-related gene family in Angelica dahurica var. formosana was systematically investigated based on "Chuanzhi No. 2" through transcriptome database search and bioinformatics and the temporal and spatial expression patterns were analyzed through real-time fluorescence-based quantitative polymerase chain reaction(PCR). The results showed that 122 MYB-related proteins family were identified, mainly including the unstable hydrophilic proteins with good thermal stability. Most of the proteins were located in nuclei. The majority of the proteins had the structures of random coil and α-helix. Five MYB-related proteins family of A. dahurica var. formosana had membrane-binding domains. The conserved domain analysis of MYB-related proteins family of A. dahurica var. formosana showed that the MYB domains of genes in five subgroups, similar to 2 R-, 3 R-, and 4 R-MYB proteins, contained three evenly distributed Trp(W) residues in the MYB repeat sequence. The phylogenetic analysis of MYB-related proteins family in A. dahurica var. formosana and Arabidopsis thaliana showed that the MYB-related members were unevenly distributed in five subgroups, and A. thaliana and A. dahurica var. formosana had almost the same number of genes in the CCA1-like subgroup. There were differences in the number, type, and distribution of motifs contained in 122 encoded proteins. Transcription factors with similar branches had similar domains and motifs. The expression pattern analysis showed that the transcription factors AdMYB53, AdMYB83, and AdMYB89 responded to hormones to varying degrees, and they were highly expressed in leaves and responded quickly in roots. This study lays a foundation for further investigating the function of MYB-related transcription factors of A. dahurica var. formosana and solving the corresponding biological problems such as bolting early.
Assuntos
Angelica , Gastrópodes , Angelica/química , Animais , Biologia Computacional , Filogenia , Folhas de Planta , Proteínas de Plantas/genética , Fatores de Transcrição/genéticaRESUMO
As a member of the low-density lipoprotein receptor (LDLR) superfamily, vitellogenin (Vg) receptor (VgR) is responsible for the uptake of Vg into developing oocytes and is a potential target for pest control. Here, a full-length VgR complementary DNA (named as CsVgR) was isolated and characterized in the rice stem borer, Chilo suppressalis. The composite CsVgR gene contained an open reading frame of 5,484 bp encoding a protein of 1,827 amino acid residues. Structural analysis revealed that CsVgR contained two ligand-binding domains (LBDs) with four Class A (LDLRA ) repeats in LBD1 and seven in LBD2, which was structurally different from most non-Lepidopteran insect VgRs having five repeats in LBD1 and eight in LBD2. The developmental expression analysis showed that CsVgR messenger RNA expression was first detectable in 3-day-old pupae, sharply increased in newly emerged female adults, and reached a peak in 2-day-old female adults. Consistent with most other insects VgRs, CsVgR was exclusively expressed in the ovary. Notably, injection of dsCsVgR into late pupae resulted in fewer follicles in the ovarioles as well as reduced fecundity, suggesting a critical role of CsVgR in female reproduction. These results may contribute to the development of RNA interference-mediated disruption of reproduction as a control strategy of C. suppressalis.
Assuntos
Proteínas do Ovo/genética , Mariposas/genética , Receptores de Superfície Celular/genética , Animais , Proteínas do Ovo/química , Proteínas do Ovo/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Insetos/metabolismo , Mariposas/crescimento & desenvolvimento , Mariposas/metabolismo , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Filogenia , Interferência de RNA , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/química , Receptores de Superfície Celular/metabolismo , Análise de Sequência de ProteínaRESUMO
MicroRNAs (miRNAs) are known to fine-tune growth, development, and stress-induced responses. Osa-miR1873 is a rice-specific miRNA targeting LOC_Os05g01790. Here, we show that Osa-miR1873 fine-tunes rice immunity against Magnaporthe oryzae and yield traits via LOC_Os05g01790. Osa-miR1873 was significantly upregulated in a susceptible accession but downregulated in a resistance accession at 24 h post-inoculation (hpi) of M. oryzae. Overexpressing Osa-miR1873 enhanced susceptibility to M. oryzae and compromised induction of defense responses. In contrast, blocking Osa-miR1873 through target mimicry compromised susceptibility to M. oryzae and enhanced induction of defense responses. Altered expression of Osa-miR1873 also resulted in some defects in yield traits, including grain numbers and seed setting rate. Moreover, overexpression of the target gene LOC_Os05g01790 increased rice blast disease resistance but severely penalized growth and yield. Taken together, we demonstrate that Osa-miR1873 fine-tunes the rice immunity-growth trade-off via LOC_Os05g01790, and blocking Osa-miR1873 could improve blast disease resistance without significant yield penalty. Thus, the Osa-miR1873-LOC_Os05g01790 regulatory module is valuable in balancing yield traits and blast resistance.
Assuntos
Magnaporthe/fisiologia , MicroRNAs/metabolismo , Oryza/genética , Oryza/microbiologia , Imunidade Vegetal , Resistência à Doença/genética , Suscetibilidade a Doenças , Ecótipo , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Oryza/crescimento & desenvolvimento , Oryza/imunologia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Imunidade Vegetal/genética , Característica Quantitativa HerdávelRESUMO
miRNAs contribute to plant resistance against pathogens. Previously, we found that the function of miR398b in immunity in rice differs from that in Arabidopsis. However, the underlying mechanisms are unclear. In this study, we characterized the mutants of miR398b target genes and demonstrated that multiple superoxide dismutase genes contribute to miR398b-regulated rice immunity against the blast fungus Magnaporthe oryzae. Out of the four target genes of miR398b, mutations in Cu/Zn-Superoxidase Dismutase1 (CSD1), CSD2 and Os11g09780 (Superoxide DismutaseX, SODX) led to enhanced resistance to M. oryzae and increased hydrogen peroxide (H2 O2 ) accumulation. By contrast, mutations in Copper Chaperone for Superoxide Dismutase (CCSD) resulted in enhanced susceptibility. Biochemical studies revealed that csd1, csd2 and sodx displayed altered expression of CSDs and other superoxide dismutase (SOD) family members, leading to increased total SOD enzyme activity that positively contributed to higher H2 O2 production. By contrast, the ccsd mutant showed CSD protein deletion, resulting in decreased CSD and total SOD enzyme activity. Our results demonstrate the roles of different SODs in miR398b-regulated resistance to rice blast disease, and uncover an integrative regulatory network in which miR398b boosts total SOD activity to upregulate H2 O2 concentration and thereby improve disease resistance.
Assuntos
Resistência à Doença , Peróxido de Hidrogênio/metabolismo , MicroRNAs/metabolismo , Oryza/metabolismo , Doenças das Plantas/microbiologia , Superóxido Dismutase/metabolismo , Regulação para Baixo , Regulação da Expressão Gênica de Plantas , Magnaporthe , MicroRNAs/genética , Modelos Biológicos , Mutação/genética , Oryza/genética , Oryza/microbiologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
The chemical constituents from lipophilic parts of the stems of Celastrus monospermus were studied in this paper. The compounds were separated and purified by repeated column chromatographic methods including silica gel, ODS and Sephadex LH-20, and the structures of compounds were determined by spectral data analyses. Twenty six compounds were obtained and identified as 3-oxofriedelane(1), 3-oxofriedelan-28-al(2), 3,12-dioxofriedelane(3), 3ß-hydroxyolean-12-en(4), 3-oxo-28-hydroxyfriedelane(5), 3-oxo-29-hydroxyfriedelane(6), 3-oxo-11ß-hydroxyfriedel-ane(7), 3-oxo-16α-hydroxyfriedelane(8), 3,12-dioxo-28-hydroxyfriedelane(9), 1,3-dioxo-15α-hydroxyfriedelane(10), 3ß,6α-dihydroxyolean-12-en(11), 3-oxo-7α,26-dihydroxyfriedel-ane(12), oleanolic acid(13), 3,15-dioxofriedelane(14), 3α-friedelinol(15), 3,12-dioxofriedelan-28-al(16), 3-oxo-12α-hydroxyfriedelane(17), 3,15-dioxo-12α-hydroxyfriedelane(18), 3ß,11ß-dihydroxyolean-12-en(19), 1ß,3ß-dihydroxylupan-20(29)-en(20), 3-oxo-12α,28-dihydroxyfriedelane(21), 3ß,23-epoxyfriedelan-28-oic acid(22), salaquinone A(23), 2α,3ß-dihydroxyfriedelan-28-oic acid(24), 23-nor-6-oxodemethylpristimerol(25) and 3-oxo-friedelan-27,28-dioic acid(26). Among them, compounds 8, 10-15, 18-20, 22-26 were obtained from this plant for the first time, and compounds 8, 10, 12, 14-15, 18, 22-24, 26 were separated from the genus Celastrus for the first time.
Assuntos
Celastrus/química , Compostos Fitoquímicos/isolamento & purificação , Caules de Planta/química , Triterpenos/isolamento & purificaçãoRESUMO
Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well-defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty-seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real-time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged <1 year (P = 0.003), children without fever and wheezing (P = 0.015 and P = 0.000), days of illness <14 days (P = 0.002), children with bronchiolitis (P = 0.012) and children with RSV single infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co-infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89:589-597, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos
Metapneumovirus/isolamento & purificação , Infecções por Paramyxoviridae/patologia , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções Respiratórias/patologia , Carga Viral , Adolescente , Criança , Pré-Escolar , China , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Nasofaringe/virologia , Infecções por Paramyxoviridae/virologia , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Vírus Respiratório Sincicial/virologia , Infecções Respiratórias/virologiaRESUMO
BACKGROUND: Elderly patients have more special medical needs when compared with young ones; thus, the results of open reduction and internal fixation (ORIF) for acetabular fractures should be stratified by age in these patients. This study seeks to determine whether the age of the patient influences the results of the ORIF for acetabular fractures. METHODS: We performed a retrospective analysis of prospectively collected data on 53 elderly patients with displaced acetabular fractures who underwent ORIF between May 2004 and May 2011. Patients were divided into two groups by age: young-old group (60-74 years) and old-old group (75-90 years). The number of patients in each group was 28 and 25. The reduction quality and clinical function was evaluated using the Matta criteria and modified Postel Merle D'Aubigne Score, respectively. Operative time, bleeding amount, and complications were recorded. RESULTS: Patients in old-old group had significantly lower anatomical reduction rate (p = 0.024), less operative time (p = 0.021), and less bleeding amount (p = 0.016) than those in the young-old group. The reduction quality in the young-old group was strongly associated with clinical function (p < 0.05). However, no difference in clinical function was detected among the different reduction qualities in the old-old group (p > 0.05). Moreover, no significant difference in clinical functions (p = 0.787) and complications (p = 0.728) was detected between the two groups. CONCLUSIONS: Old-old patients may expect comparable clinical functions and complications with young-old patients. The reduction quality in old-old patients may be not significantly associated with clinical function. Different treatment strategies may be applied for acetabular fractures with ORIF in different age groups.
Assuntos
Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Fixação Interna de Fraturas/tendências , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Acetábulo/lesões , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In this study, a series of catechol-based amides (8a-n) with different amide linkers linking the catecholic moiety to the terminal phenyl ring was designed and synthesized as potent phosphodiesterase (PDE) 4D inhibitors. The inhibitory activities of these compounds were evaluated against the core catalytic domains of human PDE4 (PDE4CAT), full-length PDE4B1 and PDE4D7 enzymes, and other PDE family members. The results indicated the majority of compounds 8a-n displayed moderate to good inhibitory activities against PDE4CAT. Among these compounds, compound 8 j with a short amide linker (-CONHCH2-) displayed comparable PDE4CAT inhibitory activity (IC50=410 nM) with rolipram. More interestingly, compound 8 g, a potent and selective PDE4D inhibitor (IC50=94 nM), exhibited a 10-fold selectivity over the PDE4B subtypes and an over 1000-fold selectivity against other PDE family members. Docking simulations suggested that 8 g forms three extra H-bonds with the N-H of residue Asn487 and two water molecules.
Assuntos
Amidas/química , Catecóis/química , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/química , Desenho de Fármacos , Inibidores de Fosfodiesterase/síntese química , Inibidores de Fosfodiesterase/farmacologia , Amidas/síntese química , Amidas/metabolismo , Sítios de Ligação , Domínio Catalítico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Ativação Enzimática/efeitos dos fármacos , Humanos , Ligação de Hidrogênio , Concentração Inibidora 50 , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Simulação de Acoplamento Molecular , Inibidores de Fosfodiesterase/química , Inibidores de Fosfodiesterase/metabolismo , Ligação Proteica/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Paeoniflorin is the main active ingredient of Chinese herbaceous peony. This study is to investigate the protective effect of paeoniflorin (Pae) on acute brain damage induced by lipopolysaccharide (LPS) in mice. The mice were randomly assigned to the normal control, model control (LPS), as well as groups of paeoniflorin and lipopolysaccharide (Pae + LPS). Then the mice were administered intraperitioneally with normal saline or Pae (10, 30 mg · kg(-1)) once daily for 6 d. One hour after intrapertioneally treatment on the seventh day, each group were injected LPS (5 mg · kg(-1)) to establish the endotoxin lipopolysaccharide inflammation model except the normal group. The mice were sacrificed after 6 h and the brain homogenates were prepared and measured. The malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), succinatedehydrogenase (SDH), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase were dectected by the colorimetric method. The levels of HO-1 and Nrf2 protein in subcellular fractions of brain tissue were detected by Western blot. The results demonstrated that the administration with paeoniflorin reduced the levels of the MDA production; significantly increase the activities of antioxidant enzyme (SOD and GSH-PX). In addition, paeoniflorin could enhance the total antioxidant capacity, decrease the level of H2O2, and increase the activities of SDH, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase. Furthermore, paeoniflorin can increase the expression of HO-1 and activate the nuclear transfer of Nrf2. Taking together, these findings suggest that paeoniflorin alleviate the acute inflammation in mice brain damage induced by LPS, which is related with its antioxidant effect and improvement of energy metabolism.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Heme Oxigenase-1/genética , Lipopolissacarídeos/farmacologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
OBJECTIVE: To systematically evaluate the long-term clinical efficacy and safety of mild hypothermia therapy in neonates with hypoxic-ischemic encephalopathy (HIE). METHODS: All randomized controlled trials (RCTs) of mild hypothermia therapy for neonatal HIE from inception to March 2014 were retrieved from databases including Cochrane Library, PubMed, Embase, CBMdisc, and Wanfang Data. Meta analysis was performed using RevMan 5.1 Software. RESULTS: Eight RCTs met the search criteria. The results of Meta analysis showed that, compared with the control group, systemic hypothermia significantly reduced the mortality rate and the incidence of growth delay (RR=0.73, 95% CI: 0.61-0.89; RR=0.70, 95%CI: 0.54-0.93); selective head or systemic hypothermia therapy significantly reduced the incidence of cerebral palsy (RR=0.65, 95%CI: 0.46-0.94; RR=0.67, 95%CI: 0.52-0.86) up to 12-24 months of age. One study reported that hypothermia reduced the mortality rate and the rate of a composite end point of death or severe disability compared with the control group at 6 to 7 years of age. The incidence of adverse events including sinus bradyarrhythmia, thrombocytopenia and hypoglycemia was significantly higher in the hypothermia group than in the control group, whereas the incidence of cardiac arrhythmia, hypotension, thrombosis or bleeding, hypokalemia, sepsis, and liver dysfunction showed no significant differences between the two groups. CONCLUSIONS: Mild hypothermia therapy demonstrates a significant efficacy in children with HIE up to 12-24 months of age, but there is still a need for further research on childhood outcomes after mild hypothermia for neonatal HIE. This therapy has few adverse effects and a high clinical tolerability.