RESUMO
BACKGROUND: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. METHODS: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. RESULTS: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. CONCLUSION: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.
Assuntos
Infecções por Caliciviridae , Norovirus , Humanos , Lactente , Infecções Assintomáticas/epidemiologia , Infecções por Caliciviridae/epidemiologia , Estudos de Coortes , População do Leste Asiático , Fezes , Genótipo , Epidemiologia Molecular , Norovirus/genética , FilogeniaRESUMO
The oxidative decarboxylation of prenyl 4-hydroxybenzoate to prenylhydroquinone has been frequently proposed for the biosynthesis of prenylated (hydro)quinone derivates (sometimes meroterpenoids), yet no corresponding genes or enzymes have so far been reported. A FAD-binding monooxygenase (VibMO1) was identified that converts prenyl 4-hydroxybenzoate into prenylhydroquinone and is likely involved in the biosynthesis of vibralactones and other meroterpenoids in the basidiomycete Boreostereum vibrans. Feeding of 3-allyl-4-hydroxybenzylalcohol, an analogue of the vibralactone pathway intermediate 3-prenyl-4-hydroxybenzylalcohol, generated 20 analogues with different scaffolds. This demonstrated divergent pathways to skeletally distinct compounds initiating from a single precursor, thus providing the first insight into a novel biosynthetic pathway for 3-substituted γ-butyrolactones from a shikimate origin.
Assuntos
Basidiomycota/enzimologia , Vias Biossintéticas , Lactonas/metabolismo , Oxigenases de Função Mista/metabolismo , Basidiomycota/química , Basidiomycota/metabolismo , Descarboxilação , Hidroquinonas/metabolismo , Lactonas/análise , Parabenos/metabolismoRESUMO
Kashin-Beck disease is an endemic joint disease characterized by deep chondrocyte necrosis, and T-2 toxin exposure has been confirmed its etiology. This study investigated mechanism of T-2 toxin inducing mitochondrial dysfunction of chondrocytes through p53-cyclophilin D (CypD) pathway. The p53 signaling pathway was significantly enriched in T-2 toxin response genes from GeneCards. We demonstrated the upregulation of the p53 protein and p53-CypD complex in rat articular cartilage and ATDC5 cells induced by T-2 toxin. Transmission electron microscopy showed the damaged mitochondrial structure of ATDC5 cells induced by T-2 toxin. Furthermore, it can lead to overopening of the mitochondrial permeability transition pore (mPTP), decreased mitochondrial membrane potential, and increased reactive oxygen species generation in ATDC5 cells. Pifithrin-α, the p53 inhibitor, alleviated the increased p53-CypD complex and mitochondrial dysfunction of chondrocytes induced by T-2 toxin, suggesting that p53 played an important role in T-2 toxin-induced mitochondrial dysfunction. Mechanistically, T-2 toxin can activate the p53 protein, which can be transferred to the mitochondrial membrane and form a complex with CypD. The increased binding of p53 and CypD mediated the excessive opening of mPTP, changed mitochondrial membrane permeability, and ultimately induced mitochondrial dysfunction and apoptosis of chondrocytes.
Assuntos
Doenças Mitocondriais , Toxina T-2 , Ratos , Animais , Condrócitos/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Peptidil-Prolil Isomerase F , Ciclofilinas/genética , Ciclofilinas/metabolismoRESUMO
The underlying mechanism of fluorosis has not been fully elucidated. The purpose of this study was to explore the mechanism of fluorosis induced by sodium fluoride (NaF) using proteomics. Six offspring rats exposed to fluoride without dental fluorosis were defined as group A, 8 offspring rats without fluoride exposure were defined as control group B, and 6 offspring rats exposed to fluoride with dental fluorosis were defined as group C. Total proteins from the peripheral blood were extracted and then separated using liquid chromatography-tandem mass spectrometry. The identified criteria for differentially expressed proteins were fold change > 1.2 or < 0.83 and P < 0.05. Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the oeCloud tool. The 177 upregulated and 22 downregulated proteins were identified in the A + C vs. B group. KEGG pathway enrichment analysis revealed that transforming growth factor-ß (TGF-ß) signaling pathway significantly enriched. PPI network constructed using Cytoscape confirmed RhoA may play a crucial role. The KEGG results of genes associated with fluoride and genes associated with both fluoride and inflammation in the GeneCards database also showed that TGF-ß signaling pathway was significantly enriched. The immunofluorescence in HPA database showed that the main expression sites of RhoA are plasma membrane and cytosol, while the main expression site of Fbn1 is the Golgi apparatus. In conclusion, long-term NaF intake may cause inflammatory response in the peripheral blood of rats by upregulating TGF-ß signaling pathway, in which RhoA may play a key role.
Assuntos
Intoxicação por Flúor , Fluorose Dentária , Ratos , Animais , Fluoretos/toxicidade , Proteômica/métodos , Fluoreto de Sódio/toxicidade , Biomarcadores , Transdução de Sinais , Fator de Crescimento Transformador beta/genéticaRESUMO
INTRODUCTION: The contribution of brain abnormalities in patients with Parkinson's disease (PD) to impaired functional status remains uncertain. Our study assessed whether global and regional brain structural abnormalities are associated with impaired performance of activities of daily living (ADL) in PD patients. MATERIAL AND METHODS: A retrospective analysis was conducted of 46 patients with PD, recruited prospectively from a movement disorder clinic. Motor impairment and disability were assessed using the Hoehn and Yahr (H-Y) scale and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). Cognitive status was evaluated with Montreal Cognitive Assessment (MoCA). The performance of ADL was indexed by the sum score of the Physical Self-Maintenance Scale (PSMS) and Lawton Instrumental ADL scale. Brain magnetic resonance imaging (MRI) was performed to assess white matter hyperintensities and medial temporal lobe atrophy (MTLA). Global brain atrophy, indexed by the relative grey matter volume (RGM), relative white matter volume (RWM) and average cortical thickness of the whole brain, was quantified by voxel-based morphometry (VBM). RESULTS: The ADL score (where higher scores indicate poorer performance) negatively correlated with RWM (where greater volume indicates less severe atrophy; r = -0.41, p = 0.004) and RGM (where greater volume indicates less severe atrophy; r = -0.43, p = 0.003) but not with the average cortical thickness ( r = -0.16, p = 0.29). With ADL score as the dependent variable in a linear regression model, H-Y stage and RWM significantly correlated with the ADL score after adjusting for age and MoCA score, and together accounted for 51% of the variance therein. RGM was not significantly correlated with the ADL score after adjusting for age and MoCA score. CONCLUSIONS: Cerebral white matter atrophy may be associated with the performance of ADL in patients with PD, indicating an important role of white matter impairment in their functional status.
Assuntos
Doença de Parkinson , Substância Branca , Humanos , Atividades Cotidianas , Doença de Parkinson/patologia , Substância Branca/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Atrofia/complicações , Atrofia/patologia , Substância Cinzenta/patologiaRESUMO
Purpose: Our purpose was to assess job stress and burnout among anesthesiologists in the tertiary class A hospitals in Northwest China, analyze the possible causes and adverse consequences of increased job stress and burnout of anesthesiologists in this region, and put forward suggestions in combination with the current national policies. Methods: We sent 500 electronic questionnaires to all anesthesiologists practicing in the tertiary class A hospitals in Northwest China from 1960 to 2017 on April 2020. A total of 336 (67.2%) questionnaires were returned and could be used for analysis. Burnout and job stress were assessed by using the modified Maslach Burnout Inventory-Human Services Survey and Chinese Perceived Stress Scale, respectively. Results: First, as for emotional exhaustion, the situations of anesthesiologists with different working years and workloads are different with statistical significance (P < 0.05). Second, as for depersonalization, the situations of anesthesiologists with different ages, professional titles, working years, physical health status, and workload are different (P < 0.05). Third, as for personal accomplishment, the situations of anesthesiologists with different physical health status are different (P < 0.05). Finally, the regression results showed that the longer the fatigue working years and the worse the physical health of anesthesiologists in Northwest China, the more likely these two factors were to cause burnout (P < 0.05), as for job stress, there was a negative correlation between job stress and physical health status (P < 0.05). Conclusion: Burnout and high job pressure are common among anesthesiologists in tertiary class A hospitals in Northwest China. We should focus on the allocation of labor intensity, pay attention to the physical and mental health of employees, establish targeted incentive mechanism, and improve the system of promotion and income rises for grassroots doctors. This may be not only conducive to the quality of medical care for patients but also conducive to the development of anesthesiology in China. Trial registration: Identifier: ChiCTR2000031316.
RESUMO
Acute gastroenteritis (AGE) caused by rotavirus (RV) remains a public health issue in China. To accelerate the mass rotavirus vaccination, it is important to inform the policy maker, and the public of the economic burden caused by rotavirus infection. A meta-analysis was conducted applying standardized algorithms. Articles published before January 1, 2023, in English and Chinese were searched through PubMed, CNKI, and WanFang Data. Studies with cost analysis of RV AGE were included. A random-effects model was applied to synthesize the total cost of RV AGE from the societal perspective. A prospective survey aimed to measure the cost of RV AGE was conducted in 2021 and 2022 in Shaoxing city, Zhejiang province, that can represent the developed region. The cost data was applied as deviation indicator, in comparison with the pooled estimate generated from meta-analysis. Totally 286 articles were identified, and eventually 12 studies were included. The pooled total social cost of RV AGE was US$282.1 (95%CI: US$213.4-350.7). The pooled private cost of RV AGE was US$206.4 (95%CI: US$155.2-257.5). RV AGE hospitalized and RV AGE incurred in developed regions caused remarkable higher burden (US$631.2 [95%CI: US$512.6-749.8], and US$333.6 [95%CI: US$234.1-433.2] respectively), compared to RV AGE treated at outpatient, and incurred in less developed regions. Our study demonstrates that RV AGE causes a significant economic burden in China. Given the promising effectiveness and highly cost-effective, introduction of rotavirus vaccines in national immunization programs could substantially reduce the economic burden in China.
Assuntos
Gastroenterite , Infecções por Rotavirus , Vacinas contra Rotavirus , Humanos , Lactente , Análise Custo-Benefício , População do Leste Asiático , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Gastroenterite/virologia , Vacinação em Massa , Estudos Prospectivos , Rotavirus , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Pré-EscolarRESUMO
Previous analyses of the naphthomycin biosynthetic gene cluster and a comparison with known naphthomycin-type products from Streptomyces sp. CS have suggested that new products can be found from this strain. In this study, screening by LC-MS of Streptomyces sp. CS products formed under different culture conditions revealed several unknown peaks in the product spectra of extracts derived from oatmeal medium cultures. Three new naphthomycins, naphthomycins L (1), M (2), and N (3), and the known naphthomycins A (4), E (5), and D (6) were obtained. The structures were elucidated using spectroscopic data from 1D and 2D NMR and HRESIMS experiments.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antifúngicos/isolamento & purificação , Naftoquinonas/isolamento & purificação , Naftoquinonas/farmacologia , Streptomyces/química , Streptomyces/genética , Antibacterianos/química , Antifúngicos/química , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Família Multigênica , Naftoquinonas/químicaRESUMO
Toxic cyanobacterial blooms in freshwater have been considered as threats to human health. Microcystins are a family of cyclic polypeptides produced by cyanobacteria and are toxic to plants and animals. Microcystin-LR (MC-LR) is the most toxic variant among the microcystin family and could cause oxidative stress in various organs, including the reproduction system. The aim of this study was to investigate the effect of MC-LR on apoptosis of Sertoli cells that play an essential role in the development and maturation of sperm cells. Sertoli cells were isolated from healthy immature rats and cultured with MC-LR. The viability of Sertoli cells was decreased after treatment with MC-LR at 10 µg/ml for 24 h (P < 0.05). Moreover, the MC-LR-treated cells exhibited condensed chromatin and fragmented nuclei, features of apoptosis, as judged by Hoechst 33258 staining. We also analyzed the mRNA and protein levels of three apoptosis-related genes, p53, bax and bcl-2, using reverse transcription-polymerase chain reaction and Western blot analyses, respectively. Both p53 and bax function as promoters of apoptosis, while bcl-2 is an apoptotic suppressor. The mRNA and protein expression levels of p53 and bax were increased in Sertoli cells treated with MC-LR at 10 µg/ml compared with the control group (P < 0.05), while the bcl-2 protein levels were decreased in cells treated with MC-LR at 10 µg/ml (P < 0.05). Moreover, caspase-3 activity that is involved in the induction of apoptosis was significantly increased in Sertoli cells treated with MC-LR. These results indicate that MC-LR induces apoptosis of Sertoli cells.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Microcistinas/toxicidade , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos , Animais , Proteínas Reguladoras de Apoptose/genética , Western Blotting , Caspase 3/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Toxinas Marinhas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Células de Sertoli/enzimologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Strain DCS523 was isolated from the branch tissue of Daphniphyllum longeracemosum and determined to be a Penicillium sp. according to the ITS sequence analysis. The extracts from the PDA solid fermentation media of Penicillium sp. DCS523 were purified to give two new chroman derivatives as well as six known compounds. Based on their spectral data the new compounds were identified as (Z)-6-acetyl- 3-(1,2-dihydroxypropylidene)-5-hydroxy-8-methylchroman-2-one and 6-acetyl-2α,5- dihydroxy-2-(2-hydroxypropyl)- 3α,8-dimethylchroman, respectively.
Assuntos
Cromanos/isolamento & purificação , Penicillium/química , Sequência de Bases , Cromanos/química , Cromatografia Líquida de Alta Pressão , Primers do DNA , Espectroscopia de Ressonância Magnética , Penicillium/genética , RNA Ribossômico 5,8S/genética , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria UltravioletaRESUMO
INTRODUCTION: The efficacy of neoadjuvant nimotuzumab for gastric cancer remained controversial. We conducted a systematic review and meta-analysis to explore the efficacy of neoadjuvant nimotuzumab plus chemotherapy vs chemotherapy for gastric cancer. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2019, and included randomized controlled trials assessing the efficacy of neoadjuvant nimotuzumab plus chemotherapy vs chemotherapy for gastric cancer. This meta-analysis was performed using the random-effect model. RESULTS: Four randomized controlled trials were included in the meta-analysis. There were 128 patients included in intervention group and 131 patients included in control group. Overall, compared with chemotherapy for gastric cancer, neoadjuvant nimotuzumab plus chemotherapy showed no substantial influence on response rate (risk ratio [RR]â=â1.22; 95% CIâ=â0.78-1.89; Pâ=â.38), disease control rate (RRâ=â2.22; 95% confidence interval [CI]â=â0.32-15.40; Pâ=â.42), rash (RRâ=â1.26; 95% CIâ=â0.96-1.66; Pâ=â.10), neutropenia (RRâ=â1.26; 95% CIâ=â0.96-1.66; Pâ=â.10), anemia (RRâ=â1.08; 95% CIâ=â0.62-1.89; Pâ=â.78), or nausea (RRâ=â1.19; 95% CIâ=â0.96-1.48; Pâ=â.12), but might improve the incidence of vomiting (RRâ=â1.60; 95% CIâ=â1.03-2.50; Pâ=â.04). CONCLUSIONS: Neoadjuvant nimotuzumab might provide no additional benefits to the treatment of gastric cancer.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Terapia Neoadjuvante , Neoplasias Gástricas/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: Fatigue has been recognized as a common non-motor problem in patients with Parkinson's disease (PD). The determination of the clinical correlates of fatigue in PD patients is necessary. The purpose of this study was to explore the risk factors related to the severity of fatigue in PD. PATIENTS AND METHODS: In this study, 141 patients with PD were recruited. All patients were evaluated comprehensively, including motor function, fatigue severity scale (FSS), cognition and psychiatric status. Brain magnetic resonance imaging (MRI) examinations were performed to assess the severity of white matter hyperintensities, and the presence of silent lacunes, medial temporal lobe atrophy (MTLA), and global cortical atrophy (GCA). The crude associations of variables with FSS were examined using Pearson (nor-mally distributed) or Spearman correlation (categorical or non-normal distributed) analyses. Multiple linear regression analysis was performed to find the correlates of fatigue severity in PD patients. RESULTS: In the whole sample, with FSS as the dependent variable in a linear regression model, Hamilton Depression Rating Scale (HAM-D), GCA, female sex were significant correlates of FSS, accounting for 24% of the variance of it. When subjects with depression (HAM-D ≥ 35) were excluded, HAM-D, GCA, female sex remained significant correlates of FSS, accounting for 22% of the variance of FSS. There is no correlation between white matter hyperintensities and FSS. CONCLUSION: GCA may be an important correlate of the fatigue severity commonly observed in PD patients.
Assuntos
Córtex Cerebral/patologia , Fadiga/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Idoso , Atrofia/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
We measured the activities of six kinds of enzyme, including ß-glucosidase (BG), ß-N-acetyl-glucosaminidase (NAG), leucine aminopeptidase (LAP), acid phosphatase (AP), polyphenol oxidase (POX), peroxidase (POD), as well as enzyme stoichiometric ratios and soil physical and chemical properties at 0-10 and 10-20 cm layers across typical Pinus massoniana plantation, Pinus elliottii plantation and mixed plantation of P. massoniana and Schima superba (broadleaved-conifer mixed plantation) in mid-subtropical China. Key factors driving the variation in soil enzyme activity and stoichiometry among different stand types were investigated. The results showed that the activities of soil BG and LAP were significantly affected by stand type. Soil BG activity at 10-20 cm soil layer was significantly higher in P. elliottii plantation than in P. massoniana plantation, while the activity of LAP was highest in the P. massoniana plantation. Soil BG/(NAG+LAP) and BG/AP at 10-20 cm layer of P. elliottii plantation were significantly higher than those of P. massoniana plantation, while (NAG+LAP)/AP of P. massoniana plantation was significantly higher than those of P. elliottii plantation and mixed plantation. The vector length of enzyme stoichiometry at 10-20 cm soil layer was significantly different among stand type, with an order of P. elliottii plantation > broadleaved-conifer mixed plantation > P. massoniana. The vector angles of enzyme stoichiometry in the three plantations were greater than 45°, with the vector angle in the P. elliottii plantation at 10-20 cm soil layer being significantly greater than that of the P. massoniana plantation. Results from redundancy analysis showed that soil carbon quality index and the ratio of soil organic carbon to total phosphorus (C/P), soil water content and C/P were the key factors affecting soil enzyme activity and stoichiometry at 0-10 and 10-20 cm soil layers, respectively. The quantity and quality of soil carbon and phosphorus, and soil water content played a key role in regulating nutrient cycling in mid-subtropical plantation ecosystem.
Assuntos
Pinus , Solo , Carbono/análise , China , Ecossistema , Nitrogênio/análiseRESUMO
BACKGROUND: Mitochondrial diseases are a heterogenous group of multisystemic disorders caused by genetic mutations affecting mitochondrial oxidation function. Brain involvement is commonly found in most cases but rarely as the unique clinical manifestation. Since the knowledge of its clinical manifestation combined with genetic testing is important for preventing misdiagnosis and delay in treatment, we report here how we diagnosed and managed a very unusual case of mitochondrial encephalopathy. CASE SUMMARY: We report a 52-year-old woman with recurrent stroke-like episodes carrying the m.10158T>C mutation in the MT-ND3 gene, which is also responsible for fatal infant-onset Leigh syndrome. Despite the common mutation, the present case featured a distinct clinical and neuroimaging manifestation from Leigh syndrome. This patient presented with sudden onset of right-sided hemiparesis and hemilateral sensory disturbance accompanied by a left temporal cluster-like headache and later developed epilepsy during hospitalization, with no other signs suggestive of myopathy, lactate acidosis, or other systemic symptoms. Brain magnetic resonance imaging revealed variable lesions involving multiple cortical and subcortical regions. Furthermore, a negative genetic test obtained from peripheral blood delayed the diagnosis of mitochondrial disease, which was eventually established through second-generation DNA sequencing using biopsied muscle. CONCLUSION: Based on this report, we suggest that clinicians pursue proper genetic testing for patients when the clinical phenotype is suggestive of mitochondrial diseases.
RESUMO
OBJECTIVE: To investigate the effect of Bmi-1 gene silence on the proliferation ability of K562 cells in vitro and in vivo, and to explore the relation of molecular mechanism between proliferation ability of K562 cells in vitro and in vivo with PTEN/pAKT signaling pathway. METHODS: The Bmi-1 small interference RNA (siRNA) sequences were transfected into K562 cells for decreasing Bmi-1 expression. The effect of Bmi-1 siRNA on the proliferation of K562 cells in vitro and in vivo was detected by MTT method and colony-forming test, the effect of Bmi-1 siRNA on the tumorogenicity of K562 cells was observed by subcutaneous inoculation of K562 cells, LY294002 and Bpv treated K562 cells in nude mice, the expression of Bmi-1, PTEN and pAKT proteins were detected by Western blot. RESULTS: The Bmi-1 siRNA could inhibit the proliferation activity, colony-forming and tumor-forming abilities of K562 cells. After the silence of Bmi-1 gene, the PTEN expression in Bmi-1 gene-silenced group was significantly enhanced. While the pAKT expression in Bmi-1 gene-silenced group was significantly reduced; after the K562 cells were treated with LY294002 (an inhibitor of pAKT), the pAKT expression colony-forming and tumor forming abilities were reduced in comparison with untreated K562 cells; after the K562-S1 cells were treated with Bpv (an inhibitor of PTEN), the PTEN expression decreased, while the pAKT expression, colony forming and tumor-forming abilities were restored. CONCLUSION: The Bmi-1 gene possibly involves in regulation of K562 proliferation in vivo and in vitro, the effect of PTEN/pAKT signaling pathway maybe one of molecular mechanisms mediating this regulation.
Assuntos
Apoptose , Leucemia , Animais , Proliferação de Células , Humanos , Células K562 , Camundongos , Camundongos Nus , PTEN Fosfo-Hidrolase , Complexo Repressor Polycomb 1 , Proteínas Proto-Oncogênicas c-akt , RNA Interferente Pequeno , Transdução de SinaisRESUMO
The Isodon plants (Lamiaceae) have been used in traditional Chinese medicine to alleviate sufferings from inflammations and cancers. This feature has been attributed to the presence of pharmacologically active ent-kaurane diterpenoids such as eriocalyxin B and oridonin. The Isodon eriocalyx (Dunn) Kudô species native to southwest China can accumulate a particularly high content of ent-kaurane diterpenoids (â¼1.5% w/w of dried leaves). We previously identified diterpene synthases IeCPS1 and IeCPS2 as ent-copalyl diphosphate synthases (ent-CPS) potentially involved in Isodon ent-kaurane diterpenoids biosynthesis. In this study, analysis of RNA-seq transcriptome of the I. eriocalyx plant revealed three other diterpene synthase genes (IeCPS3, IeKS1, and IeKSL1). Their functional characterization through coupled in vitro enzyme assays has confirmed that IeCPS3 is an ent-CPS specifically producing ent-copalyl diphosphate (ent-CPP). IeKS1 accepted ent-CPP to produce exclusively ent-kaurene and may thus be defined as an ent-kaurene synthase (ent-KS). When IeKSL1 was combined with IeCPS2 or IeCPS3, no product was detected. Based on tissue-specific expression and metabolic localization studies, the IeCPS3 and IeKS1 transcripts were significantly accumulated in leaves where the ent-kaurane diterpenoid eriocalyxin B dominates, whereas weak expression of both were observed in germinating seeds in which gibberellin biosynthetic pathway is normally active. Our findings suggest that both IeCPS3 and IeKS1 possess dual roles in general (gibberellins) and specialized diterpenoid metabolism, such as that of the Isodon ent-kaurane diterpenoids.
Assuntos
Alquil e Aril Transferases/metabolismo , Diterpenos/metabolismo , Isodon/metabolismo , Proteínas de Plantas/metabolismo , Alquil e Aril Transferases/genética , Clonagem Molecular , Diterpenos/química , Diterpenos do Tipo Caurano/metabolismo , Giberelinas/biossíntese , Isodon/química , Isodon/genética , Filogenia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Plantas Medicinais/metabolismoRESUMO
BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is effective against advanced Parkinson's disease (PD), allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China. METHODS: Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinson's Disease Rating Scale Part III (UPDRS III), Parkinson's Disease Questionnatire-39, Parkinson's Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures. RESULTS: In the "off" state (off medication), DBS improved UPDRS III scores by 35.87% in 5 years, compared with preoperative baseline (P < 0.001). In the "on" state (on medication), motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% (P < 0.001) from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 ± 210.1 mg at baseline to 310.6 ± 158.4 mg at 5 years (by 52.96%, P < 0.001). The average pulse width, frequency and amplitude at 5 years were 75.0 ± 18.21 µs, 138.5 ± 19.34 Hz, and 2.68 ± 0.43 V, respectively. CONCLUSIONS: STN DBS is an effective intervention for PD, although associated with a slightly diminished efficacy after 5 years. Compared with other studies, patients in our study required lower voltage and medication for satisfactory symptom control.