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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 1-6, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027244

RESUMO

OBJECTIVE: To investigate the efficacy and safety of arsenic trioxide combined with ATRA and chemo- therapy for treatment of relapsed acute promyelocytic leukemia (APL) patients. METHODS: The clinic data of 25 patients with relapse APL treated in our hospital from 1996 to 2013 were collected and analyzed. Among the 25 patients, 15 patients suffered first-time hematological relapse (HR), and the other 10 patients showed first-time molecular relapse (MR). The patients with first-time replase were treated with ATO+ATRA+Anthracycline re-induction chemotherapy. The clinical features, complete remission (CR) rate, overall survival (OS), disease-free survival (DFS) and adverse events after re-induction therapy were analyzed. RESULTS: Fourteen of 15 hematological relapsed patients achieved the second-time hematological complete remission (CR2) after re-induction therapy except one patient died of bleeding complication during the re-induction. 8 of 14 patient showed molecular complete remission (CRm) after two cycles of therapy with this regimen. Totally, eleven out of the 14 HR patients were alive without disease till the last follow-up, and 3 of the 14 HR patients died because of bleeding complications. All of the 10 molecular relapsed patients received the second CRm after treated by the regimen. Among these 10 patients, 6 patients suffered only once relapse and continued with the molecular CR2 status, and for the other 4 patients with more than two-relapses, only 1 survived untill 89.3 months after achieved second-time CRm, and other 3 patients died because of bleeding complications. CONCLUSION: For relapsed APL patients, the treatment with ATO+ATRA+chemotherapy regimen after relapse still shows encouraging efficacy, no matter whether or not the application of ATO in the previous regimens. In addition, patients with more than two molecular relapses show a poor prognosis.

2.
J Ethnopharmacol ; 253: 112656, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32035217

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shegan-Mahuang Decoction (SMD), also named Yakammaoto or Shegan-Mahuang Tang, is a classic formula of traditional Chinese medicine with nine herbs, including Asarum sieboldii Miq., Aster tataricus L.f., Ephedra sinica Stapf, Belamcanda chinensis (L.) Redouté, Pinellia ternata (Thunb.) Breit., Schisandra chinensis (Turcz.) Baill., Tussilago farfara L., Zingiber officinale Roscoe, and Ziziphus jujuba Mill. SMD was originally discovered by Zhang Zhongjing in Eastern Han dynasty. It has been widely used as traditional medicine to treat flu-like symptoms in China and Japan for around twenty centuries. It was also utilized for the treatment of the early stage of acute asthma. However, the immune mechanisms underlying its therapeutic effects remain unknown. AIM OF THE STUDY: This study was set to investigate the effects of SMD on asthmatic airway hyperresponsiveness and its impacts on adaptive immunity in a mouse model of asthma. MATERIALS AND METHODS: The HPLC fingerprint profile of the water extract of SMD recorded 22 peaks, including those equivalent to guanosine, chlorogenic acid, tectoridin, 6-gingerol and wuweizisu B, as described previously (Yen et al., 2014). Airway hyperresponsiveness was assessed by measuring the airway resistance. Cellular infiltration was measured via H&E staining and immunochemistry while gene expression was analyzed using real-time RT-PCR. Treg frequency was determined through flow analysis whereas cytokine production in the supernatant was evaluated using ELISA. Finally, mTOR and NF-kB signalings were analyzed via Western blotting. RESULTS: We found that SMD largely corrected the imbalance of Th cell subsets in asthmatic mice with a significant inhibition of Th2 and Th17 cytokine production, thereby reducing asthmatic airway hyperresponsiveness. Moreover, lung function tests showed that SMD reduced airway hyperresponsiveness while immunohistochemical analyses demonstrated that SMD attenuated pulmonary infiltration of CD3+ and CD4+ T cells. Further, we observed a significant increase in the proportion of CD4+Foxp3+ Tregs in SMD-treated asthmatic mice. We also found that SMD downregulated gene expression of GATA3 and ROR-γt in murine lung tissue. In addition, both mTOR- and NF-kB-related protein expressions were reduced in the lung tissue of SMD-treated mice. SMD inhibited Th2/Th17 cytokine production by CD4+ T cells and also their mTOR activity in vitro. CONCLUSIONS: Our findings demonstrate that SMD attenuates asthmatic airway hyperresponsiveness by hindering Th2/Th17 differentiation, promoting CD4+FoxP3+ Treg generation and suppressing mTOR and NF-kB activities.

3.
Int J Biol Macromol ; 141: 41-50, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31476391

RESUMO

In this study, the reaction conditions of sulfur trioxide-pyridine (SO3-Pyr) method for the modification of Qingke ß-glucans (THB) were optimized by response surface methodology, and effects of different degrees of substitution (low, medium, and high) on the physicochemical properties, antioxidant activities, and in vitro hypolipidemic activities of THB were investigated. The optimal reaction conditions to obtain the high degree of substitution of sulfated ß-glucans were as follows: ratio of SO3-Pyr to THB of 16.88 g/g, reaction time of 2.03 h, and reaction temperature of 57.54 °C. Results showed that sulfated modification significantly affected the water solubilities, apparent viscosities, molecular weights, and molar ratios of constituent monosaccharides of THB. Besides, the sulfated THB exhibited much better antioxidant activities (DPPH and nitric oxide radical scavenging activities, and reducing powers), in vitro binding properties (fat, cholesterol, and bile-acid binding capacities), and pancreatic lipase inhibition activities than that of THB. Indeed, the sulfated THB with higher degree of substitution has stronger antioxidant activities and in vitro hypolipidemic activities. Results suggested that the sulfated modification could be an efficient approach for the improvement of functional properties of THB, and sulfated THB could be further explored as functional food ingredients for industrial applications.

4.
Cell ; 178(6): 1329-1343.e12, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31447177

RESUMO

Assembly of Kaposi's sarcoma-associated herpesvirus (KSHV) begins at a bacteriophage-like portal complex that nucleates formation of an icosahedral capsid with capsid-associated tegument complexes (CATCs) and facilitates translocation of an ∼150-kb dsDNA genome, followed by acquisition of a pleomorphic tegument and envelope. Because of deviation from icosahedral symmetry, KSHV portal and tegument structures have largely been obscured in previous studies. Using symmetry-relaxed cryo-EM, we determined the in situ structure of the KSHV portal and its interactions with surrounding capsid proteins, CATCs, and the terminal end of KSHV's dsDNA genome. Our atomic models of the portal and capsid/CATC, together with visualization of CATCs' variable occupancy and alternate orientation of CATC-interacting vertex triplexes, suggest a mechanism whereby the portal orchestrates procapsid formation and asymmetric long-range determination of CATC attachment during DNA packaging prior to pleomorphic tegumentation/envelopment. Structure-based mutageneses confirm that a triplex deep binding groove for CATCs is a hotspot that holds promise for antiviral development.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 637-640, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204910

RESUMO

OBJECTIVE: To explore the clinical features and therapeutic efficacy in adult ALL patients with t (1; 19) (E2A-PBX1). METHODS: The clinic data of 19 adult ALL patients with t (1; 19) (E2A-PBX1) in our hospital from Nov. 22, 2010 to Apr. 4, 2018 were collected. The clinical features,complete remission (CR) rate, overall survival (OS) rate and relapse-free survival (RFS) rate of patients received chemotherapy and chemotherapy+HSCT were analyzed. RESULTS: In all the 19 patients, the median age was 24 (14-66), median WBC count was 16.47×109 (1.8-170.34)/L, median Hb level was 98 (65-176) g/L, median Plt count was 50 (15-254)×109/L. Pre B-ALL were 17 cases (89.5%), and common B-ALL were 2 cases (10.5%). Patients received the induction therapy, the overall CR rate was 94.7%, one course CR rate was 94.7%, 4 year OS rate was 47.1% and RFS rate was 43.3%. The OS rate and RFS rate of patients received transplantation were slightly higher than those of patients not received transplantation (OS: 62.5% vs 36.7%) (P=0.188);RFS (62.5% vs 38.9%) (P=0.166). CONCLUSION: Most adult ALL patients with t (1; 19) (E2A-PBX1) is Pre B-ALL by Immunophenotyping, as compared with the pediatric patients, the therapeutic efficacy for adult patients with t (1; 19) (E2A-PBX1) is worsen, therefore, stem cell transplantation is still acquired for better long term survival.


Assuntos
Proteínas de Homeodomínio/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 19 , Humanos , Imunofenotipagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Indução de Remissão
6.
Polymers (Basel) ; 11(5)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086008

RESUMO

In the present study, an improved fluorometric assay based on aniline blue dye for the specific, accurate, and rapid quantification of 1,3-ß-glucans in edible mushrooms was developed and fully validated. Furthermore, the improved method was successfully applied for the quantitative evaluation of water soluble 1,3-ß-glucans extracted from Dictyophora indusiata by ultrasound-assisted extraction (UAE) with response surface methodology. Results showed that the improved method exhibited high specificity, accuracy, precision, repeatability, and stability, as well as a wide calibration range of 10-600 µg/mL (R2 > 99.9%). The maximum extraction yields of water soluble 1,3-ß-glucans (1.20%) and total polysaccharides (5.41%) were achieved at the optimized extraction parameters as follows: ultrasound amplitude (56%), ultrasound extraction time (15 min), and ratio of liquid to raw material (22 mL/g). The results suggest that the improved fluorometric assay has great potential to be used as a routine method for the quantitative evaluation of 1,3-ß-glucans in edible mushrooms and that the UAE method is effective for the extraction of 1,3-ß-glucans from edible mushrooms.

7.
Nature ; 570(7760): 257-261, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31142842

RESUMO

Herpesviruses are enveloped viruses that are prevalent in the human population and are responsible for diverse pathologies, including cold sores, birth defects and cancers. They are characterized by a highly pressurized pseudo-icosahedral capsid-with triangulation number (T) equal to 16-encapsidating a tightly packed double-stranded DNA (dsDNA) genome1-3. A key process in the herpesvirus life cycle involves the recruitment of an ATP-driven terminase to a unique portal vertex to recognize, package and cleave concatemeric dsDNA, ultimately giving rise to a pressurized, genome-containing virion4,5. Although this process has been studied in dsDNA phages6-9-with which herpesviruses bear some similarities-a lack of high-resolution in situ structures of genome-packaging machinery has prevented the elucidation of how these multi-step reactions, which require close coordination among multiple actors, occur in an integrated environment. To better define the structural basis of genome packaging and organization in herpes simplex virus type 1 (HSV-1), we developed sequential localized classification and symmetry relaxation methods to process cryo-electron microscopy (cryo-EM) images of HSV-1 virions, which enabled us to decouple and reconstruct hetero-symmetric and asymmetric elements within the pseudo-icosahedral capsid. Here we present in situ structures of the unique portal vertex, genomic termini and ordered dsDNA coils in the capsid spooled around a disordered dsDNA core. We identify tentacle-like helices and a globular complex capping the portal vertex that is not observed in phages, indicative of herpesvirus-specific adaptations in the DNA-packaging process. Finally, our atomic models of portal vertex elements reveal how the fivefold-related capsid accommodates symmetry mismatch imparted by the dodecameric portal-a longstanding mystery in icosahedral viruses-and inform possible DNA-sequence recognition and headful-sensing pathways involved in genome packaging. This work showcases how to resolve symmetry-mismatched elements in a large eukaryotic virus and provides insights into the mechanisms of herpesvirus genome packaging.


Assuntos
Microscopia Crioeletrônica , Empacotamento do DNA , Genoma Viral , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/ultraestrutura , Conformação de Ácido Nucleico , Capsídeo/química , Capsídeo/ultraestrutura , DNA Viral/química , DNA Viral/ultraestrutura , Herpesvirus Humano 1/química , Modelos Moleculares , Vírion/química , Vírion/genética , Vírion/ultraestrutura
8.
Int J Biol Macromol ; 135: 274-281, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31128186

RESUMO

In order to explore polysaccharides from loquat leaves (LLPs) as functional food ingredients for prevention and treatment of obesity and type 2 diabetes, the physicochemical characteristics, in vitro binding properties, and inhibitory effects on α-amylase and α-glucosidase of polysaccharides from the leaves of different loquat cultivars, including 'Baiyu', 'Chuannong8', 'Yuanbao', and 'Dawuxing', were investigated and compared. Results showed that the contents of total uronic acids and degree of esterification in LLPs ranged from (27.04 ±â€¯1.76)% to (41.46 ±â€¯1.91)%, and from (20.54 ±â€¯0.11)% to (26.90 ±â€¯0.10)%, respectively. The weight-average molecular weights of LLPs ranged from 4.307 × 106 Da to 5.101 × 106 Da, and the major constituent monosaccharides of LLPs were rhamnose, galacturonic acid, arabinose, and galactose. Furthermore, LLPs exerted strong in vitro fat binding, cholesterol binding, and bile acid binding capacities, as well as remarkable inhibitory effects on α-amylase and α-glucosidase, which might be attributed to their molecular weights, molecular weight distributions, and degree of esterification. Results are helpful for better understanding of chemical structures and bioactivities of polysaccharides from loquat leaves, and LLPs had good potential to be explored as functional food ingredients for prevention and treatment of obesity and type 2 diabetes.


Assuntos
Fenômenos Químicos , Eriobotrya/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/química
9.
Curr Opin Struct Biol ; 54: 152-160, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30904821

RESUMO

Neuronal synapses are key devices for transmitting and processing information in the nervous system. Synaptic plasticity, generally regarded as the cellular basis of learning and memory, involves changes of subcellular structures that take place at the nanoscale. High-resolution imaging methods, especially electron microscopy (EM), have allowed for quantitative analysis of such nanoscale structures in different types of synapses. In particular, the semi-ordered organization of neurotransmitter receptors and their interacting scaffolds in the postsynaptic density have been characterized for both excitatory and inhibitory synapses by studies using various EM techniques such as immuno-EM, electron tomography of high-pressure freezing and freeze-substituted samples, and cryo electron tomography. These techniques, in combination with new correlative approaches, will further facilitate our understanding of the molecular organization underlying diverse functions of neuronal synapses.

10.
Trials ; 20(1): 3, 2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606237

RESUMO

BACKGROUND: Cough variant asthma (CVA) is one of the leading causes of chronic coughing. The main treatment is currently anti-inflammatory medication. However, the coughing may return or be aggravated and lung function may deteriorate once the anti-inflammatory treatment is stopped. The effect of Chinese herbal medicine (CHM) on chronic coughing is remarkable, but high-quality evidence supporting its effectiveness is still lacking. This trial aims to evaluate the safety and efficacy, especially the long-term efficacy, of CHM plus anti-inflammatory medications for the treatment of CVA. METHODS/DESIGN: A randomized placebo-controlled double-blind trial will be conducted. It will consist of a 3-month intervention followed by a 6-month follow-up period. The target sample size is 60 patients with CVA who are between 18 and 70 years old. The eligible subjects will be allocated randomly into the experimental or control group in a ratio of 1:1. Patients in the experimental group will take CHM granules (4.9 g twice daily), while patients in the control group will be given a matched placebo. An administration of salmeterol/fluticasone propionate combination for 12 weeks will be the basic therapy for the two groups. The primary outcome is the cough visual analog scales (CVAS). The secondary outcomes include quality of life, rate of symptom relapse, lung function, and blood tests. A safety assessment will also be performed during the trial. DISCUSSION: The evidence gathered by the trial will be a valuable addition to informing treatment options for patients with CVA. TRIAL REGISTRATION: http://www.chictr.org.cn , ID: ChiCTR-IOR-16009148. Registered on 3 September 2016.


Assuntos
Asma/tratamento farmacológico , Tosse/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Seguimentos , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1269-1274, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30295237

RESUMO

OBJECTIVE: To evaluate the efficacy of primary prophylaxis of voriconazole against invasive infection of pulmonary aspergillosis (IPA) during remission-induction chemotherapy (RIC) of patients with acute myeloid leukemia (AML). METHODS: Clinical data of 102 de novo AML patients who received primary anti-IPA prophylaxis during the first induction chemotherapy were analyzed retrospectively. All the cases were divided into voriconazole-treated group and posaconazole-treated group according to the prophylactic agent. The incidences of IPA and systemic antifungal treatment during induction chemotherapy were analyzed for both groups. RESULTS: Among 102 enrolled cases, 42 cases received voriconazole and other 60 received posaconazole as primary prophylaxis. IPA occurred in 3 cases of voriconazole group (1 probable, 2 possible); IPA occurred in 4 cases of posaconazose group, and all were possible cases. The incidence of IPA during remission-induction chemotherapy in variconazole group equaled to posaconazose group (7.1% vs. 6.7%) (P=0.925). Beside IPA cases, 2 cases in voriconazole group and 4 cases in posaconazole group received intravenous anti aspergillosis drugs preemptive treatment, and no significant difference of prophylactic success rate was observed between two groups (88.1% vs. 86.7%) (P=0.831). Visual disturbance was the most common adverse event occurred in voriconazole group, but no significant differences of incidences of other adverse effects were observed when compared with posaconazole group. CONCLUSION: According to similar prophylactic effect with posaconazole, voriconazole appears to be a good alternative for primary prophylaxis of IPA during remission-induction chemotherapy in AML patients.


Assuntos
Leucemia Mieloide Aguda , Aspergilose Pulmonar , Antifúngicos , Humanos , Quimioterapia de Indução , Micoses , Estudos Retrospectivos , Voriconazol
13.
Front Neuroanat ; 12: 48, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29942253

RESUMO

The morphology and function of neuronal synapses are regulated by neural activity, as manifested in activity-dependent synapse maturation and various forms of synaptic plasticity. Here we employed cryo-electron tomography (cryo-ET) to visualize synaptic ultrastructure in cultured hippocampal neurons and investigated changes in subcellular features in response to chronic inactivity, a paradigm often used for the induction of homeostatic synaptic plasticity. We observed a more than 2-fold increase in the mean number of dense core vesicles (DCVs) in the presynaptic compartment of excitatory synapses and an almost 20-fold increase in the number of DCVs in the presynaptic compartment of inhibitory synapses after 2 days treatment with the voltage-gated sodium channel blocker tetrodotoxin (TTX). Short-term treatment with TTX and the N-methyl-D-aspartate receptor (NMDAR) antagonist amino-5-phosphonovaleric acid (AP5) caused a 3-fold increase in the number of DCVs within 100 nm of the active zone area in excitatory synapses but had no significant effects on the overall number of DCVs. In contrast, there were very few DCVs in the postsynaptic compartments of both synapse types under all conditions. These results are consistent with a role for presynaptic DCVs in activity-dependent synapse maturation. We speculate that these accumulated DCVs can be released upon reactivation and may contribute to homeostatic metaplasticity.

14.
J Food Drug Anal ; 26(2): 688-695, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29567239

RESUMO

The serious cytotoxicity of tyramine attracted marked attention as it induced necrosis of human intestinal cells. This paper presented a novel and facile high performance thin-layer chromatography (HPTLC) method tailored for screening tyramine in cheese. Separation was performed on glass backed silica gel plates, using methanol/ethyl acetate/ammonia (6/4/1 v/v/v) as the mobile phase. Special efforts were focused on optimizing conditions (substrate preparation, laser wavelength, salt types and concentrations) of surface enhanced Raman spectroscopy (SERS) measurements directly on plates after derivatization, which enabled molecule-specific identification of targeted bands. In parallel, fluorescent densitometry (FLD) scanning at 380

Assuntos
Queijo/análise , Cromatografia em Camada Delgada/métodos , Densitometria/métodos , Microscopia Óptica não Linear/métodos , Tiramina/análise , Análise de Alimentos/métodos , Sensibilidade e Especificidade
15.
J Neurosci ; 38(6): 1493-1510, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29311144

RESUMO

As key functional units in neural circuits, different types of neuronal synapses play distinct roles in brain information processing, learning, and memory. Synaptic abnormalities are believed to underlie various neurological and psychiatric disorders. Here, by combining cryo-electron tomography and cryo-correlative light and electron microscopy, we distinguished intact excitatory and inhibitory synapses of cultured hippocampal neurons, and visualized the in situ 3D organization of synaptic organelles and macromolecules in their native state. Quantitative analyses of >100 synaptic tomograms reveal that excitatory synapses contain a mesh-like postsynaptic density (PSD) with thickness ranging from 20 to 50 nm. In contrast, the PSD in inhibitory synapses assumes a thin sheet-like structure ∼12 nm from the postsynaptic membrane. On the presynaptic side, spherical synaptic vesicles (SVs) of 25-60 nm diameter and discus-shaped ellipsoidal SVs of various sizes coexist in both synaptic types, with more ellipsoidal ones in inhibitory synapses. High-resolution tomograms obtained using a Volta phase plate and electron filtering and counting reveal glutamate receptor-like and GABAA receptor-like structures that interact with putative scaffolding and adhesion molecules, reflecting details of receptor anchoring and PSD organization. These results provide an updated view of the ultrastructure of excitatory and inhibitory synapses, and demonstrate the potential of our approach to gain insight into the organizational principles of cellular architecture underlying distinct synaptic functions.SIGNIFICANCE STATEMENT To understand functional properties of neuronal synapses, it is desirable to analyze their structure at molecular resolution. We have developed an integrative approach combining cryo-electron tomography and correlative fluorescence microscopy to visualize 3D ultrastructural features of intact excitatory and inhibitory synapses in their native state. Our approach shows that inhibitory synapses contain uniform thin sheet-like postsynaptic densities (PSDs), while excitatory synapses contain previously known mesh-like PSDs. We discovered "discus-shaped" ellipsoidal synaptic vesicles, and their distributions along with regular spherical vesicles in synaptic types are characterized. High-resolution tomograms further allowed identification of putative neurotransmitter receptors and their heterogeneous interaction with synaptic scaffolding proteins. The specificity and resolution of our approach enables precise in situ analysis of ultrastructural organization underlying distinct synaptic functions.


Assuntos
Microscopia Crioeletrônica/métodos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Sinapses/fisiologia , Tomografia/métodos , Animais , Moléculas de Adesão Celular/metabolismo , Feminino , Processamento de Imagem Assistida por Computador , Neurônios/fisiologia , Neurônios/ultraestrutura , Densidade Pós-Sináptica/metabolismo , Gravidez , Ratos , Receptores de GABA-A/metabolismo , Receptores de GABA-A/ultraestrutura , Receptores de Glutamato/metabolismo , Receptores de Glutamato/ultraestrutura , Sinapses/ultraestrutura , Vesículas Sinápticas/fisiologia , Vesículas Sinápticas/ultraestrutura
16.
J Gen Virol ; 98(11): 2837-2849, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29035172

RESUMO

Inside the virions of α-herpesviruses, tegument protein pUL25 anchors the tegument to capsid vertices through direct interactions with tegument proteins pUL17 and pUL36. In addition to promoting virion assembly, both pUL25 and pUL36 are critical for intracellular microtubule-dependent capsid transport. Despite these essential roles during infection, the stoichiometry and precise organization of pUL25 and pUL36 on the capsid surface remain controversial due to the insufficient resolution of existing reconstructions from cryo-electron microscopy (cryoEM). Here, we report a three-dimensional (3D) icosahedral reconstruction of pseudorabies virus (PRV), a varicellovirus of the α-herpesvirinae subfamily, obtained by electron-counting cryoEM at 4.9 Å resolution. Our reconstruction resolves a dimer of pUL25 forming a capsid-associated tegument complex with pUL36 and pUL17 through a coiled coil helix bundle, thus correcting previous misinterpretations. A comparison between reconstructions of PRV and the γ-herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) reinforces their similar architectures and establishes important subfamily differences in the capsid-tegument interface.


Assuntos
Herpesvirus Suídeo 1/química , Herpesvirus Suídeo 1/ultraestrutura , Multimerização Proteica , Proteínas Estruturais Virais/análise , Proteínas Estruturais Virais/ultraestrutura , Vírion/química , Vírion/ultraestrutura , Microscopia Crioeletrônica , Imagem Tridimensional , Ligação Proteica
17.
Antiviral Res ; 144: 34-43, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28461072

RESUMO

Rosmarinic acid-4-O-ß-D-glucoside (RAG) is a dicaffeoyl phenolic compound isolated from Sarcandra glabra (Thunb.) Nakai. Preliminary studies show that RAG has significant anti-inflammatory properties and can alleviate ear swelling in mice and the paw swelling in rats. Here, the anti-influenza effects of RAG were investigated in mice infected with A/FM/1/47 H1N1 virus. The survival rate and body weight were observed, the lung edema, virus copies, inflammatory cytokines (including IL-4, IL-5, TNF-α and IFN-γ) and oxidative damage indexes (including SOD, MDA, NO, and CAT) were measured. Moreover, immune cell recruitment in alveoli was measured with white blood cells and differential counts. Therapeutic RAG concentrations substantially improve the symptoms, mitigate body weight loss and alleviate lung edema induced by virus, thus improve survival protection effects. Furthermore, RAG was shown to regulate influenza virus-induced inflammatory cytokine expression, specifically by downregulating the Th1 cell cytokines IFN-γ, TNF-α and upregulating the Th2 cell cytokines IL-4, IL-5. Cell migration and infiltration were also diminished after RAG administration.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios não Esteroides/administração & dosagem , Cinamatos/administração & dosagem , Depsídeos/administração & dosagem , Glucosídeos/administração & dosagem , Infecções por Orthomyxoviridae/complicações , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios não Esteroides/química , Peso Corporal , Cinamatos/química , Citocinas/análise , Depsídeos/química , Modelos Animais de Doenças , Glucosídeos/química , Pulmão/patologia , Pulmão/virologia , Camundongos , Infecções por Orthomyxoviridae/patologia , Análise de Sobrevida , Carga Viral
18.
J Food Sci ; 82(3): 594-604, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28182839

RESUMO

The objective of this research was to investigate the effects of different modified casings and storage time on the quality attributes of cooked sausages using principal component analysis (PCA) and discriminant analysis. The effects of modifying different casing treatments on sausages' color (L* , a* , b* ), pH, and texture (hardness, springiness, cohesion, gumminess, chewiness) after 36-d storage were estimated by PCA. According to the PCA, lightness at day 36 was correlated to sample stuffed in casing with treatment 2 (T2; soy lecithin concentration: 1:27.5, soy oil concentration: 1.25%, lactic acid concentration: 19.5 mL/kg NaCl [solid], residence time: 75 min). T2 sample can be distinguished from control sample at days 1, 8, 15, and 36 according to electronic nose system. DA was performed to determine possible different sample groups according to selected variables. Results showed that chewiness was the best discriminator for differentiating sausages stored for 15 d from other days. Chewiness and gumminess were able to discriminate sausages stuffed in casing with T2 from control sample. The relationships between modified concentrations and quality attributes of cooked sausages after 36-d storage were also established.


Assuntos
Manipulação de Alimentos/métodos , Conservação de Alimentos/métodos , Ácido Láctico , Lecitinas , Produtos da Carne/análise , Tensoativos , Compostos Orgânicos Voláteis/análise , Animais , Cor , Culinária , Armazenamento de Alimentos , Dureza , Humanos , Soja , Suínos
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(6): 1615-1621, 2016 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-28024465

RESUMO

OBJECTIVE: To evaluate the influence of FLT3-ITD mutation on long term survival of newly diagnosed patients with acute promyelocytic leukemia (APL). METHODS: Long term survival of 170 newly diagnosed APL patients was retrospective analyzed. Mutation rate of FLT3-ITD was assayed, and its influence on disease-free survival(DFS) or overall survival (OS) was analyzed. RESULTS: The mutation rate of FLT3-ITD in newly diagnosed patients with APL was 14.1%. WBC count at diagnosis was higer in FLT3-ITD positive group than that in negative group, and the mutation rate of FLT3-ITD was highest in high risk group. Induction death rate in FLT3-ITD positive and negative group were 12.5% and 2.9%, respectively (P=0.031). Complete remission(CR) rate in 2 groups were 83.3% and 97.1%(P=0.004). The 5-year OS rates in 2 groups were 87.5±6.8% and 90.6±2.6% (P=0.740). The 5-year DFS in 2 groups were 82.8±9.1% and 83.6±3.4%(P=0.928). CONCLUSION: FLT3-ITD mutation is related with high peripheral white blood cell count in APL, the APL with FLT3-ITD mutation has higher induction death rate and lower CR rate than those in that without FLT3-ITD mutation, but FLT3-ITD mutation did not affect on long term DFS and OS.


Assuntos
Leucemia Promielocítica Aguda , Intervalo Livre de Doença , Humanos , Leucemia Mieloide Aguda , Contagem de Leucócitos , Mutação , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Tirosina Quinase 3 Semelhante a fms
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(2): 300-5, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25948175

RESUMO

OBJECTIVE: To investigate the incidence of karyotypes and gene mutations for elder acute myeloid leukemia and to explore the relationship between each other. METHODS: Clinical data and bone marrow samples of elder AML patients were collected. Karyotype and gene mutation (FLT3, NPM1, C-Kit, CEBPα, DNMT3A) test were performed, characteristics of karyotypes and gene mutations were analysed. RESULTS: The incidence of better risk karyotype was 16.6%, in which the incidences of t(15;17), t(8;21) and inv (16)/t(16;16) were 3.90%, 10.73%, and 1.95% respectively; the incidence of intermediate risk karyotype was 72.2%, in which the incidence of normal karyotype was 57.86%; the incidence of poor risk karyotype was 11.20%, in which the incidence of of MLL/11q23, complex karyotype and monosomal karyotype were 1.95%, 6.34%, 5.85% respectively; the incidences of FLT3, NPM1, C-Kit, CEBPα, DNMT3A mutation were 12.57%, 22.06%, 2.16%, 14.71%, 15.71% respectively. Compared with patients older than 60 years, patients with age of 55-60 years were with less complex karyotype (1.09% vs 10.62%)(P=0.003) and monosomal karyotype (2.17% vs 8.85%)(P=0.032), and more t(8;21)(17.39% vs 5.31%)(P=0.008) and inv (16)/t(16;16)(4.35% vs 0.00%)(P=0.045). CONCLUSION: For older AML patients, great difference in the distribution of karyotyes was found between the patients older than 60 years and patients with age of 55-60 years, while no such characteristics was found for gene mutations. Good elucidation of karyotypes and gene mutations are key for the treatment of older acute myeloid leukemia patients.


Assuntos
Cariótipo , Mutação , Humanos , Incidência , Cariotipagem , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-kit
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