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This study established an ultra-performance liquid chromatography(UPLC) fingerprint of abandoned stems and leaves of Artemisia selengensis and quantitative analysis of multi-components by single marker(QAMS) for five phenolic acid components. Waters Acquity UPLC BEH C_(18) chromatography column(2.1 mm×100 mm, 1.7 µm) was used. The gradient elution was carried out with the mobile phase composed of 0.1% phosphoric acid water and acetonitrile at a flow rate of 0.3 mL·min~(-1) and a column temperature at 30 â. The detection wavelength was 330 nm, and the injection volume was 2 µL. Similarity evaluation and cluster analysis were conducted on the fingerprint data, and 15 common components in 13 batches of abandoned stems and leaves of A. selengensis were identified. The relative correction factors of ferulic acid, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C were calculated using chlorogenic acid as the internal reference. The QAMS for determining five components in the abandoned stems and leaves of A. selengensis was established. At the same time, the content of these five components was determined using the external standard method(ESM), and the results showed that there were no significant differences in their content determined by the QAMS and the ESM. The results indicated that the content of phenolic acid components in the abandoned stems and leaves of A. selengensis from different varieties and different origins had obvious differences. In addition, the content of phenolic acid components in the abandoned stems and leaves of lignified A. selengensis was significantly higher than that of non-lignified A. selengensis. In summary, QAMS established in this study can be quickly, accurately, and economically used to determine the content of five phenolic acid components in abandoned stems and leaves of A. selengensis, laying a foundation for the resource development and utilization of abandoned stems and leaves of A. selengensis.
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Artemisia , Hidroxibenzoatos , Folhas de Planta , Caules de Planta , Controle de Qualidade , Folhas de Planta/química , Caules de Planta/química , Artemisia/química , Cromatografia Líquida de Alta Pressão/métodos , Hidroxibenzoatos/análise , Hidroxibenzoatos/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análiseRESUMO
Genes and environmental conditions are thought to interact in the development of postnatal brain in schizophrenia (SZ). Genome wide association studies have identified that PPARGC1A being one of the top candidate genes for SZ. We previously reported GABAergic neuron-specific PGC-1α knockout mice (Dlx5/6-Cre:PGC-1αfl/fl) presented some characteristic features of SZ. However, there is a fundamental gap of the molecular mechanism by which PGC-1α gene involved in the developmental trajectory to SZ. To explore whether PGC-1α regulates environmental factors interacting with genetic susceptibility to trigger symptom onset and disease progression, PGC-1α deficient mice were utilized to model genetic effect and an additional oxidative stress was induced by GBR injection. We confirm that PGC-1α gene deletion prolongs critical period (CP) timing, as revealed by delaying maturation of PV interneurons (PVIs), including their perineuronal nets (PNNs). Further, we confirm that gene × environment (G × E) influences CP plasticity synergistically and the interaction varies as a function of age, with the most sensitive period being at preweaning stage, and the least sensitive one at early adult age in PGC-1α deficient mice. Along this line, we find that the synergic action of G × E is available in ChABC-infusion PGC-1α KO mice, even though during the adulthood, and the neuroplasticity seems to remain open to fluctuate. Altogether, these results refine the observations made in the PGC-1α deficient mice, a potential mouse model of SZ, and illustrate how PGC-1α regulates CP plasticity via G × E interaction in the developmental trajectory to SZ.
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Neurônios GABAérgicos/metabolismo , Interneurônios/metabolismo , Parvalbuminas/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Esquizofrenia/metabolismo , Animais , Condroitina ABC Liase/farmacologia , Interação Gene-Ambiente , Giro do Cíngulo/citologia , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Microscopia Eletrônica de Varredura , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Plasticidade Neuronal/genética , Plasticidade Neuronal/fisiologia , Estresse Oxidativo/fisiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/deficiência , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Puberdade/metabolismo , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , DesmameRESUMO
BACKGROUND: Recently the expression patterns of several cytochrome P450 (CYP) genes in different human osteoblast models were reported. However, the various expression patterns of CYPs in human osteoblasts during different stages of osteogenic differentiation have not been investigated and the effect of inflammatory cytokines on CYPs expression in osteoblasts is unknown. METHODS: The expression levels of nine different CYP genes in the human osteoblast cell line MG63 and in primary human osteoblasts (HOB) during osteogenic differentiation with or without treatment with tumor necrosis factor-α (TNFα) were analyzed by quantitative real-time PCR. RESULTS: The expression levels of most CYPs under study show a significant time dependence during osteogenic differentiation. Overall, more highly significant CYP expression level changes occur in HOB than in MG63 cells. Treatment with TNFα causes a variety of CYP expression level changes in both HOB and MG63 cells. CONCLUSIONS: Our findings indicate that TNFα treatment reduces steroid hormone production in MG63 cells (but not in HOB) at the level of lanosterol-demethylation during cholesterol biosynthesis. By contrast, TNFα treatment of HOB cells (but not in MG63) leads to the upregulation of several key enzymes involved in the biosynthesis of sex steroids, which is proposed to lead to higher levels of estrogen production. These data also suggest that at least with respect to the topic of this study the cell line MG63 is not a good representative for osteoblasts and that it is preferential to use primary osteoblasts instead.
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Sistema Enzimático do Citocromo P-450/genética , Osteoblastos/metabolismo , Osteogênese/genética , Adulto , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND: The classical human leucocyte antigen (HLA) genes were the most important genetic determinant for Graves' disease (GD). The aim of the study was to fine map causal variants of the HLA genes. METHODS: We applied imputation with a Pan-Asian HLA reference panel to thoroughly investigate themajor histocompatibility complex (MHC) associations with GD down to the amino acid level of classical HLA genes in 1468 patients with GD and 1490 controls of Han Chinese. RESULTS: The strongest finding across the HLA genes was the association with HLA-DPß1 position 205 (Pomnibus=2.48×10-33). HLA-DPA1*02:02 was the strongest association among the classical HLA alleles, which was in perfect linkage disequilibrium with HLA-DPα1 residue Met11 (OR=1.90, Pbinary=1.76×10-31). Applying stepwise conditional analysis, we identified amino acid position 205 in HLA-DPß1, position 66 and 99 in HLA-B and position 28 in HLA-DRß1 explain majority of the MHC association to GD risk. We further evaluated risk of two clinical subtypes of GD, namely persistent thyroid stimulating hormone receptor antibody -positive (pTRAb+) group and 'non-persistent TRAb positive' (pTRAb-) group after antithyroid drug therapy. We found that HLA-B residues Lys66-Arg69-Val76 could drive pTRAb- GD risk alone, while HLA-DPß1 position 205, HLA-B position 69 and 199 and HLA-DRß1 position 28 drive pTRAb+ GD risk. The risk heterogeneity between pTRAb+ and pTRAb- GD might be driven by HLA-DPα1 Met11. CONCLUSIONS: Four amino acid positions could account for the associations of MHC with GD in Han Chinese. These distinct HLA association patterns indicated the two subtypes have distinct molecular mechanisms of pathogenesis.
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Povo Asiático/genética , Doença de Graves/genética , Complexo Principal de Histocompatibilidade/genética , Fosfoproteínas/genética , Polimorfismo de Nucleotídeo Único/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Modelos MolecularesRESUMO
BACKGROUND: Recent studies have found that plant derived microRNA can cross-kingdom regulate the expression of genes in humans and other mammals, thereby resisting diseases. Can exogenous miRNAs cross the blood-prostate barrier and entry prostate then participate in prostate disease treatment? METHODS: Using HiSeq sequencing and RT-qPCR technology, we detected plant miRNAs that enriched in the prostates of rats among the normal group, BPH model group and rape bee pollen group. To forecast the functions of these miRNAs, the psRobot software and TargetFinder software were used to predict their candidate target genes in rat genome. The qRT-PCR technology was used to validate the expression of candidate target genes. RESULTS: Plant miR5338 was enriched in the posterior lobes of prostate gland of rats fed with rape bee pollen, which was accompanied by the improvement of BPH. Among the predicted target genes of miR5338, Mfn1 was significantly lower in posterior lobes of prostates of rats in the rape bee pollen group than control groups. Further experiments suggested that Mfn1 was highly related to BPH. CONCLUSIONS: These results suggesting that plant-derived miR5338 may involve in treatment of rat BPH through inhibiting Mfn1 in prostate. These results will provide more evidence for plant miRNAs cross-kingdom regulation of animal gene, and will provide preliminary theoretical and experimental basis for development of rape bee pollen into innovative health care product or medicine for the treatment of BPH.
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Proteínas de Membrana/antagonistas & inibidores , MicroRNAs/farmacologia , Proteínas Mitocondriais/antagonistas & inibidores , Pólen , Próstata/efeitos dos fármacos , Hiperplasia Prostática/metabolismo , RNA de Plantas/farmacologia , Animais , Abelhas , Peso Corporal/efeitos dos fármacos , Masculino , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Tamanho do Órgão/efeitos dos fármacos , RNA de Plantas/farmacocinética , RatosRESUMO
Cytochromes P450 (CYPs) are important for bone homeostasis, but only limited information is available on their expression in human bone cells. We analyzed the expression levels of eight CYPs in osteoblasts cultured in human bone pieces, in osteoblasts differentiated from human periosteum mesenchymal stem cells, in primary human osteoblasts and in the human osteoblast cell line MG63, respectively. Our results confirm previous reports about the presence of CYP11A1, CYP17A1, CYP24A1 and CYP27B1, while demonstrating expression of CYP2E1, CYP26A1, CYP39A1 and CYP51A1 for the first time. However, expression patterns in the four models were remarkably different from each other.
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Modelos Biológicos , Osteoblastos/metabolismo , Células Cultivadas , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Osteoblastos/citologia , Reação em Cadeia da PolimeraseRESUMO
Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. It can influence proliferation, motility, and invasiveness of cancer cells in vitro and in vivo. However, the role of the propofol in the lung cancer cells remains unclear. In this study, we demonstrated the effects of propofol on the proliferation and the apoptosis of lung cancer cell H460 by using colony formation assay and flow cytometry. Propofol also decreased tumor size and weight in established xenografted tumors. Furthermore, propofol-induced endoplasmic reticulum (ER) stress was determined by Western blot.
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Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Propofol/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologiaRESUMO
OBJECTIVE: To find and clone new antigen genes from the lambda-ZAP cDNA expression library of adult Clonorchis sinensis, and determine the immunological characteristics of the recombinant proteins. METHODS: The cDNA expression library of adult C. sinensis was screened by pooled sera of clonorchiasis patients. The sequences of the positive phage clones were compared with the sequences in EST database, and the full-length sequence of the gene (Cs22 gene) was obtained by RT-PCR. cDNA fragments containing 2 and 3 times tandem repeat sequences were generated by jumping PCR. The sequence encoding the mature peptide or the tandem repeat sequence was respectively cloned into the prokaryotic expression vector pET28a (+), and then transformed into E. coli Rosetta DE3 cells for expression. The recombinant proteins (rCs22-2r, rCs22-3r, rCs22M-2r, and rCs22M-3r) were purified by His-bind-resin (Ni-NTA) affinity chromatography. The immunogenicity of rCs22-2r and rCs22-3r was identified by ELISA. To evaluate the immunological diagnostic value of rCs22-2r and rCs22-3r, serum samples from 35 clonorchiasis patients, 31 healthy individuals, 15 schistosomiasis patients, 15 paragonimiasis westermani patients and 13 cysticercosis patients were examined by ELISA. To locate antigenic determinants, the pooled sera of clonorchiasis patients and healthy persons were analyzed for specific antibodies by ELISA with recombinant protein rCs22M-2r and rCs22M-3r containing the tandem repeat sequences. RESULTS: The full-length sequence of Cs22 antigen gene of C. sinensis was obtained. It contained 13 times tandem repeat sequences of EQQDGDEEGMGGDGGRGKEKGKVEGEDGAGEQKEQA. Bioinformatics analysis indicated that the protein (Cs22) belonged to GPI-anchored proteins family. The recombinant proteins rCs22-2r and rCs22-3r showed a certain level of immunogenicity. The positive rate by ELISA coated with the purified PrCs22-2r and PrCs22-3r for sera of clonorchiasis patients both were 45.7% (16/35), and 3.2% (1/31) for those of healthy persons. There was no cross reaction with sera of schistosomiasis and cysticercosis patients. The cross reaction with sera of paragonimiasis westermani patients was 1/15. The recombinant proteins rCs22M-2r and rCs22M-3r which only contained tandem repeats were specifically recognized by pooled sera of clonorchiasis patients. CONCLUSION: The Cs22 antigen gene of Clonorchis sinensis is obtained, and the recombinant proteins have certain diagnostic value. The antigenic determinant is located in tandem repeat sequences.
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Antígenos de Helmintos/genética , Clonorchis sinensis/genética , Clonorchis sinensis/imunologia , Sequências de Repetição em Tandem , Animais , Gatos , Clonagem Molecular , Biblioteca Gênica , Humanos , Soros Imunes , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Peroxisome proliferator-activated receptor PPARγ coactivator-α (PGC-1α) is concentrated in inhibitory interneurons and plays a vital role in neuropsychiatric diseases. We previously reported some characteristic features of schizophrenia (SZ) in GABAergic neuron-specific Pgc-1alpha knockout (KO) mice (Dlx5/6-Cre: Pgc-1alphaf/f). However, there is a fundamental gap in the molecular mechanism by which the Pgc-1alpha gene is involved in the neurobehavioral abnormalities of SZ. The loss of critical period (CP) triggers-maturations of parvalbumin interneurons (PVIs) and brakes-and the formation of perineuronal nets (PNNs) implicates mistimed trajectories during adult brain development. In this study, using the Pgc-1alpha KO mouse line, we investigated the association of Pgc-1alpha gene deletion with SZ-like behavioral deficits, PVI maturation, PNN integrity and synaptic ultrastructure. These findings suggest that Pgc-1alpha gene deletion resulted in a failure of CP onset and closure, thereby prolonging cortical plasticity timing. To determine whether the manipulation of the PNN structure is a potential method of altering neuronal plasticity, GM6001, a broad-spectrum matrix metalloproteinase (MMP)-inhibitor was applied. Here we confirmed that the treatment could effectively correct the CP plasticity window and ameliorate the synaptic ultrastructure in the Pgc-1alpha KO brain. Moreover, the intervention effect on neuronal plasticity was followed by the rescue of short-term habituation deficits and the mitigation of aberrant salience, which are some characteristic features of SZ. Taken collectively, these findings suggest that the role of PGC-1α in regulating cortical plasticity is mediated, at least partially, through the regulation of CP onset/closure. Strategically introduced reinforcement of molecular brakes may be a novel preventive therapy for psychiatric disorders associated with PGC-1α dysregulation.
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A systematic chemical study of the secondary metabolites of the marine fungus, Penicillium chrysogenum (No. Y20-2), led to the isolation of 21 compounds, one of which is new (compound 3). The structures of the 21 compounds were determined by conducting extensive analysis of the spectroscopic data. The pro-angiogenic activity of each compound was evaluated using a zebrafish model. The results showed that compounds 7, 9, 16, and 17 had strong and dose-dependent pro-angiogenic effects, with compound 16 demonstrating the strongest pro-angiogenic activity, compounds 6, 12, 14, and 18 showing moderate activity, and compounds 8, 13, and 19 exhibiting relatively weak activity.
Assuntos
Penicillium chrysogenum , Penicillium , Animais , Penicillium chrysogenum/química , Penicillium chrysogenum/metabolismo , Peixe-Zebra , Penicillium/química , Estrutura MolecularRESUMO
OBJECTIVE: To evaluate four candidate variable number tandem repeat (VNTR) loci for genotyping Mycobacterium tuberculosis complex strains. METHODS: Genomic sequences for two M. tuberculosis strains (CCDC5079 and CCDC5180) were generated, and using published sequence data, four candidate VNTR loci were identified. The VNTRs were used to genotype 225 Chinese clinical M. tuberculosis complex strains. The discriminatory power of the VNTRs was evaluated using BioNumerics 5.0 software. RESULTS: The Hunter-Gaston Index (HGI) for BJ1, BJ2, BJ3, and BJ4 loci was 0.634, 0.917, 0.697, and 0.910, respectively. Combining all four loci gave an HGI value of 0.995, thus confirming that the genotyping had good discriminatory power. The HGI values for BJ1, BJ2, BJ3, and BJ4, obtained from Beijing family strain genotyping, were 0.447, 0.878, 0.315, and 0.850, respectively. Combining all four loci produced an HGI value of 0.988 for genotyping the Beijing family strains. We observed unique patterns for M. bovis and M. africanum strains from the four loci. CONCLUSION: We have shown that the four VNTR loci can be successfully used for genotyping M. tuberculosis complex strains. Notably, these new loci may provide additional information about Chinese M. tuberculosis isolates than that currently afforded by established VNTR loci typing.
Assuntos
Técnicas de Genotipagem , Repetições Minissatélites , Mycobacterium tuberculosis/genética , Análise por Conglomerados , Humanos , Mycobacterium bovis/genéticaRESUMO
The technology of long reads substantially improved the contingency of the genome assembly, particularly resolving contiguity of the repetitive regions. By integrating the interactive fragment using Hi-C, and the HiFi technique, a solid genome of the honeybee Apis mellifera carnica was assembled at the chromosomal level. A distinctive pattern of genes involved in social evolution was found by comparing it with social and solitary bees. A positive selection was identified in genes involved with cold tolerance, which likely underlies the adaptation of this European honeybee subspecies in the north hemisphere. The availability of this new high-quality genome will foster further studies and advances on genome variation during subspeciation, honeybee breeding and comparative genomics.
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Vancomycin remains the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This study assessed risk factors for vancomycin failure in 63 patients with MRSA pneumonia through detailed clinical, microbiological, pharmacokinetic/pharmacodynamic, and genetic analyses of prospective multicenter studies conducted from February 2012 to July 2018. Therapeutic drug monitoring was performed during vancomycin treatment, and the 24-h area under the curve (AUC0-24) was calculated. All baseline strains were collected for MIC determination, heterogeneous vancomycin-intermediate S. aureus (hVISA) screening, and biofilm determination. Whole-genome sequencing was performed on the isolates to analyze their molecular typing and virulence and adhesion genes. Clinical signs and symptoms improved in 44 patients (44/63, 69.8%), with vancomycin daily dose (P = 0.045), peak concentration (P = 0.020), and sdrC (P = 0.047) being significant factors. Isolates were eradicated in 51 patients (51/63, 81.0%), with vancomycin daily dose (P = 0.009), cardiovascular disease (P = 0.043), sequence type 5 (ST5; P = 0.017), tst (P = 0.050), and sec gene (P = 0.044) associated with bacteriological failure. Although the AUC0-24/MIC was higher in the groups with bacterial eradication, the difference was not statistically significant (P = 0.108). Multivariate analysis showed that no variables were associated with clinical efficacy; ST5 was a risk factor for bacterial persistence (adjusted odds ratio, 4.449; 95% confidence interval, 1.103 to 17.943; P = 0.036). ST5 strains had higher frequencies of the hVISA phenotype, biofilm expression, and presence of some adhesion and virulence genes such as fnbB, tst, and sec than non-ST5 strains. Our study suggests that ST5 is a possible predictor of bacterial persistence in MRSA pneumonia treated with vancomycin. IMPORTANCE Few studies have simultaneously examined the influence of clinical characteristics of patients with pneumonia, the vancomycin pharmacokinetic/pharmacodynamic (PK/PD) index, and the phenotypic and genetic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains. We assessed risk factors for vancomycin failure in patients with MRSA pneumonia by analyzing these influences in a prospective multicenter study. Sequence type 5 (ST5) was a possible predictor of bacterial persistence in adult patients with MRSA pneumonia (adjusted odds ratio, 4.449). We found that this may be related to ST5 strains having higher levels of vancomycin heterogeneous resistance, biofilms, and the presence of adhesion and virulence genes such as fnbB, tst, and sec.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Pneumonia , Infecções Estafilocócicas , Humanos , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Estudos Prospectivos , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pneumonia/tratamento farmacológicoRESUMO
Lactic acid bacteria that exist in the urinogenital system play an important role in maintaining the health of the host. Here, we report the finished and annotated genome of a Lactococcus strain that was isolated from the vaginas of healthy women and shows probiotic properties, including nisin A production and adhesion to vaginal epithelial cells.
Assuntos
DNA Bacteriano/química , DNA Bacteriano/genética , Genoma Bacteriano , Lactococcus lactis/genética , Análise de Sequência de DNA , Aderência Bacteriana , Células Epiteliais/microbiologia , Feminino , Humanos , Lactococcus lactis/isolamento & purificação , Dados de Sequência Molecular , Nisina/metabolismo , Probióticos , Vagina/microbiologiaRESUMO
OBJECTIVES: Percutaneous catheter drainage (PCD) is usually performed to treat acute pancreatitis complicated by infected walled-off necrosis (WON). Insufficient drainage of infected WON may lead to a prolonged recovery process. Here, we introduce a modified PCD strategy that uses the triple guidance of choledochoscopy, ultrasonography, and computed tomography (CUC-PCD) to improve the therapeutic efficiency. METHODS: This study retrospectively analysed 73 patients with acute pancreatitis-related WON from January 2015 to January 2021. The first 38 patients were treated by ultrasonography/computed tomography-guided PCD (UC-PCD), and the next consecutive 35 patients by CUC-PCD. Perioperative data, procedural technical information, treatment outcomes, and follow-up data were collected. RESULTS: Demographic characteristics were statistically comparable between the two treatment groups (p > 0.05). After 48 h of PCD treatment, the CUC-PCD group achieved a significantly smaller size of the infected WON (p = 0.023), lower inflammatory response indexes (p = 0.020 for white blood cells, and p = 0.031 for C-reactive protein), and severity scores than the UC-PCD group (p < 0.05). Less catheter duration (p = 0.001), hospitalisation duration (p = 0.000), and global costs (p = 0.000) were observed in the CUC-PCD group compared to the UC-PCD group. There were no differences between the two groups regarding the rate of complications. CONCLUSIONS: CUC-PCD is a safe and efficient approach with potential clinical applicability for treating infected WON owing to its feasibility in placing the drainage catheter at the optimal location in real time and performing primary necrosectomy without sinus tract formation and enlargement.
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Recent evidence has confirmed the association of glucocorticoid receptor (GR) gene variants with the "stress" endocrine axis in postpartum depression (PPD). Sirtuin 1(SIRT1) is an NAD+-dependent histone deacetylase and transcriptional enhancer of GR. However, to date, the function of the SIRT1 gene in the regulation of GR expression in PPD remains to be fully determined. A hormone-stimulated pregnancy (HSP) and subsequent "postpartum" withdrawal of estrogen was employed to mimic the fluctuations in estradiol associated with pregnancy and postpartum. We confirmed that estradiol benzoate withdrawal (EW)-rats displayed depression- and anxiety-like behaviors. These behavioral dysfunctions are associated with attenuated expression of SIRT1 and GR in the hippocampus. To assess the role of SIRT1, as well as its regulatory target directly, a selective SIRT1 activator (SRT2104) was infused into the hippocampus of EW-rats. We found that pharmacological activation of hippocampal SIRT1 blocks the development of depression-related, but not anxiety-related, phenotypes of PPD. In addition, the activation of SIRT1 leads to an increase in hippocampal GR expression in EW-rats. We further confirmed that SIRT1 physically interacts with GR in a glucocorticoid-dependent manner. Taken together, our results suggest that neuropathology in PPD is caused, at least in part, by the inhibition of the SIRT1-GR signaling pathway. Elevating SIRT1 levels, either pharmacologically or through other means, could represent a therapeutic strategy for PPD.
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Depressão Pós-Parto/metabolismo , Receptores de Glucocorticoides/metabolismo , Sirtuína 1/metabolismo , Animais , Feminino , Células HEK293 , Hipocampo/metabolismo , Humanos , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Receptores de Glucocorticoides/genética , Sirtuína 1/genética , Regulação para CimaRESUMO
Bifidobacteria, known as probiotic bacteria, are high-G+C Gram-positive bacteria which naturally inhabit the human gastrointestinal tract and vagina. Recently, we completely sequenced Bifidobacterium longum JDM301, which is a widely used Chinese commercial strain with several probiotic properties.
Assuntos
Bifidobacterium/genética , Bifidobacterium/metabolismo , Genoma Bacteriano , Dados de Sequência MolecularRESUMO
OBJECTIVE: To investigate the effect of 90% portal branch ligation on liver regeneration and expression of metalloproteinases and tissue inhibitors of metalloproteinases in rats. METHODS: Ninety-six SD rats were randomly divided into Sham-PBL group and portal vein branches ligation group. The weight of both ligated and unligated lobes of liver were measured at post operation day (POD) 0.5, 1, 3, 5, 7, 14, 21 and 28. The morphological changes of the non-ligated liver lobes were observed by microscope. The expression of PCNA, MMP2, MMP9 and TIMP2 of the non-ligated liver lobes were studied by immunohistochemistry. RESULTS: 1) 95.8% rats survived from the ligation of 90% portal branch. Hepatic lobe at the ligated side diminished progressively after ligation, whereas the lobes of the unligated side underwent compensatory regeneration. The ratio of non-ligated lobes weight to the whole liver increased slowly within 1d, speeded up significantly during 1-5d period, increased slowly after POD5, and got the plateau stag at POD7; 2) PCNA index were markedly increased within POD 0.5-3 (P < 0.01). It reached the peak at POD5 and decreased slightly at POD7, but still higher than Sham-PBL group level, then gradually returned to normal. 3) The expression of MMP2,MMP9 and TIMP2 in the non-ligated liver lobes were markedly increased at 1d. It reached the peak at POD7 and gradually returned to normal within POD7-28. 4) The MMP2 and PCNA in liver had a positive correlation at POD 0.5, 1, 5, 7, 14. The expressions of MMP9 and PCNA had a positive correlation at POD 0.5, 1, 7, 21. CONCLUSION: The expressions of TIMP2 and PCNA had a positive correlation at POD1, 7, 14, 21. The expression of MMP2, MMP9 and TIMP2 of the non-ligated liver lobes is markedly increased at POD1. It reaches the peak at POD7, and dropped to normal level gradually. The expressions of MMP2, MMP9 and TIMP2 and PCNA were correlated in 90% portal branch Ligation rats. The expression of MMP2,MMP9 and TIMP2 may play a pivotal role in liver regeneration.
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Regeneração Hepática , Fígado/metabolismo , Veia Porta/cirurgia , Animais , Ligadura , Fígado/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-2/metabolismoRESUMO
The aerobatic maneuvers of swifts could be very useful for micro aerial vehicle missions. Rapid arrests and turns would allow flight in cluttered and unstructured spaces. However, these decelerating aerobatic maneuvers have been difficult to demonstrate in flapping wing craft to date because of limited thrust and control authority. Here, we report a 26-gram X-wing ornithopter of 200-millimeter fuselage length capable of multimodal flight. Using tail elevation and high thrust, the ornithopter was piloted to hover, fly fast forward (dart), turn aerobatically, and dive with smooth transitions. The aerobatic turn was achieved within a 32-millimeter radius by stopping a dart with a maximum deceleration of 31.4 meters per second squared. In this soaring maneuver, braking was possible by rapid body pitch and dynamic stall of wings at relatively high air speed. This ornithopter can recover to glide stability without tumbling after a 90-degree body flip. We showed that the tail presented a strong stabilizing moment under high thrust, whereas the wing membrane flexibility alleviated the destabilizing effect of the forewings. To achieve these demands for high thrust, we developed a low-loss anti-whirl transmission that maximized thrust output by the flapping wings to 40 grams in excess of body weight. By reducing the reactive load and whirl, this indirect drive consumed 40% less maximum electrical power for the same thrust generation than direct drive of a propeller. The triple roles of flapping wings for propulsion, lift, and drag enable the performance of aggressive flight by simple tail control.
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Apis cerana is one of the main honeybee species in artificial farming, which is widely distributed in Asian countries. The genome of A. cerana has been sequenced by several different research groups using second generation sequencing technologies. However, it is still necessary to obtain more complete and accurate genome sequences. Here we present a chromosome-scale assembly of the A. cerana genome using single-molecule real-time (SMRT) Pacific Biosciences sequencing and high-throughput chromatin conformation capture (Hi-C) genome scaffolding. The updated assembly is 215.67 Mb in size with a contig N50 of 4.49 Mb, representing an 212-fold improvement over the previous Illumina-based version. Hi-C scaffolding resulted in 16 pseudochromosomes occupying 97.85% of the assembled genome sequences. A total of 10,741 protein-coding genes were predicted and 9,627 genes were annotated. Besides, 314 new genes were identified compared to the previous version. The improved high-quality A. cerana reference genome will provide precise sequence information for biological research of A. cerana.