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1.
Sci Rep ; 14(1): 9529, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664433

RESUMO

The aim of this study was to develop a dynamic nomogram combining clinical and imaging data to predict malignant brain edema (MBE) after endovascular thrombectomy (EVT) in patients with large vessel occlusion stroke (LVOS). We analyzed the data of LVOS patients receiving EVT at our center from October 2018 to February 2023, and divided a 7:3 ratio into the training cohort and internal validation cohort, and we also prospectively collected patients from another stroke center for external validation. MBE was defined as a midline shift or pineal gland shift > 5 mm, as determined by computed tomography (CT) scans obtained within 7 days after EVT. A nomogram was constructed using logistic regression analysis, and its receiver operating characteristic curve (ROC) and calibration were assessed in three cohorts. A total of 432 patients were enrolled in this study, with 247 in the training cohort, 100 in the internal validation cohort, and 85 in the external validation cohort. MBE occurred in 24% (59) in the training cohort, 16% (16) in the internal validation cohort and 14% (12) in the external validation cohort. After adjusting for various confounding factors, we constructed a nomogram including the clot burden score (CBS), baseline neutrophil count, core infarct volume on CTP before EVT, collateral index, and the number of retrieval attempts. The AUCs of the training cohorts were 0.891 (95% CI 0.840-0.942), the Hosmer-Lemeshow test showed good calibration of the nomogram (P = 0.879). And our nomogram performed well in both internal and external validation data. Our nomogram demonstrates promising potential in identifying patients at elevated risk of MBE following EVT for LVOS.


Assuntos
Edema Encefálico , Procedimentos Endovasculares , AVC Isquêmico , Nomogramas , Trombectomia , Humanos , Masculino , Feminino , Trombectomia/efeitos adversos , Trombectomia/métodos , Idoso , Edema Encefálico/etiologia , Edema Encefálico/diagnóstico por imagem , AVC Isquêmico/cirurgia , AVC Isquêmico/etiologia , AVC Isquêmico/diagnóstico por imagem , Pessoa de Meia-Idade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Fatores de Risco , Curva ROC , Idoso de 80 Anos ou mais , Tomografia Computadorizada por Raios X
2.
Heliyon ; 10(3): e24746, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38318012

RESUMO

Objective: Half of the patients with acute large artery occlusion (LAO) have poor outcomes after endovascular treatment (EVT). Early complications such as cerebral edema and symptomatic intracranial hemorrhage (sICH) can lead to early neurological deterioration (END), which correlates with hemodynamics. This study aimed to identify the hemodynamic predictors of END and outcomes in LAO patients after EVT. Methods: A total of 76 patients with anterior circulation LAO who underwent EVT and received transcranial Doppler (TCD) monitoring were included. Bilateral middle cerebral artery (MCA) blood flow velocities (BFVs) were measured repeatedly within 1 week. Mean flow velocities (MFV) and MFV index (ipsilateral MFV/contralateral MFV) were calculated. The primary outcome was the incidence of END within 72 h. The secondary outcome was the functional outcome at 90 days-a good outcome was defined as a modified Rankin scale (mRS) score of 0-2, while a poor outcome was defined as an mRS score of 3-6. Results: A total of 13 patients (17.1 %) experienced END within 72 h, including 5 (38.5 %) with cerebral edema, 5 (38.5 %) with sICH, and 3 (23.0 %) with infarct progression. Multivariable logistic regression analysis showed that a higher 24 h MFV index was independently associated with END (aOR 10.5; 95 % CI 2.28-48.30, p = 0.003) and a poor 90-day outcome (aOR 5.10; 95 % CI 1.38-18.78, p = 0.014). The area under the receiver operating characteristic (ROC) curve (AUC) of the 24 h MFV index for predicting END was 0.807 (95 % CI 0.700-0.915, p = 0.0005), the sensitivity was 84.6 %, and the specificity was 66.7 %. At the 1-week TCD follow-up, patients who had poor 90-day outcomes showed significantly higher 1-week iMFV [73.5 (58.4-99.0) vs. 57.7 (45.3-76.3), p = 0.004] and MFV index [1.24 (0.98-1.57) vs.1.0 (0.87-1.15) p = 0.007]. A persistent high MFV index (PHMI) was independently associated with a poor outcome (aOR 7.77, 95 % CI 1.81-33.3, p = 0.006). Conclusion: TCD monitoring within 24 h after EVT in LAO patients can help predict END, while dynamic follow-up within 1 week is valuable in predicting clinical outcomes.

3.
CNS Neurosci Ther ; 30(4): e14513, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37953498

RESUMO

OBJECTIVE: To explore the relationship between asymmetric deep cerebral venous (ADCV) filling and poor outcomes after endovascular treatment (EVT) in patients with acute basilar artery occlusion (ABAO). METHODS: ABAO patients were selected from a prospectively collected data at our center. The DCV filling was evaluated using computed tomography perfusion (CTP)-derived reconstructed 4D-DSA or mean venous map. ADCV filling was defined as the internal cerebral vein (ICV), thalamostriate vein (TSV), or basal vein of Rosenthal (BVR) presence of ipsilateral filling defects or delayed opacification compared to the contralateral side. Poor prognosis was defined as a modified Rankin scale score >3 at the 90-day follow-up. RESULTS: A total of 90 patients were enrolled in the study, with a median Glasgow Coma Scale of 6, 46 (51.1%) showed ADCV filling, 59 (65.6%) had a poor prognosis, and 27 (30.7%) had malignant cerebellar edema (MCE). Multivariate adjusted analysis revealed significant associations between asymmetric TSV and poor prognosis (odds ratio, 9.091, p = 0.006); asymmetric BVR (OR, 9.232, p = 0.001) and asymmetric ICV (OR, 4.028, p = 0.041) were significantly associated with MCE. CONCLUSION: Preoperative ADCV filling is an independent influencing factor for the poor outcome after EVT in ABAO patients.


Assuntos
Arteriopatias Oclusivas , Edema Encefálico , Veias Cerebrais , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Artéria Basilar/cirurgia , Arteriopatias Oclusivas/patologia , Arteriopatias Oclusivas/cirurgia , Terapia Trombolítica/métodos , Trombectomia/métodos , Veias Cerebrais/diagnóstico por imagem , Veias Cerebrais/patologia , Edema Encefálico/patologia , Procedimentos Endovasculares/métodos , Resultado do Tratamento , Acidente Vascular Cerebral/patologia , Estudos Retrospectivos
4.
J Neuroimaging ; 34(2): 241-248, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38018876

RESUMO

BACKGROUND AND PURPOSE: Parenchymal hematoma is a dreaded complication of mechanical thrombectomy after acute ischemic stroke. This study evaluated whether blood-brain barrier permeability measurements based on CT perfusion could be used as predictors of parenchymal hematoma after successful recanalization and compared the predictive value of various permeability parameters in patients with acute ischemic stroke. METHODS: We enrolled 53 patients with acute ischemic stroke who underwent mechanical thrombectomy and achieved successful recanalization. Each patient underwent CT, CT angiography, and CT perfusion imaging before treatment. We used relative volume transfer constant (rKtrans ) values, relative permeability-surface area product (rP·S), and relative extraction fraction (rE) to evaluate preoperative blood-brain barrier permeability in the delayed perfusion area. RESULTS: Overall, 22 patients (37.7%) developed hemorrhagic transformation after surgery, including 10 patients (16.9%) with hemorrhagic infarction and 11 patients (20.8%) with parenchymal hematoma. The rP·S, rKtrans , and rE of the hypoperfusion area in the parenchymal hematoma group were significantly higher than those in the hemorrhagic infarction and no-hemorrhage transformation groups (p < .01). We found that rE and rP·S were superior to rKtrans in predicting parenchymal hematoma transformation after thrombectomy (P·S area under the curve [AUC] .844 vs. rKtrans AUC .753, z = 2.064, p = .039; rE AUC .907 vs. rKtrans AUC .753, z = 2.399, p = .017). CONCLUSIONS: Patients with parenchymal hematoma after mechanical thrombectomy had higher blood-brain barrier permeability in hypoperfusion areas. Among blood-brain barrier permeability measurement parameters, rP·S and rE showed better accuracy for parenchymal hematoma prediction.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Barreira Hematoencefálica/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , AVC Isquêmico/complicações , Trombectomia/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Hematoma/diagnóstico por imagem , Hematoma/cirurgia , Infarto/complicações , Permeabilidade , Isquemia Encefálica/cirurgia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
5.
Nature ; 621(7980): 840-848, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37674084

RESUMO

In both cancer and infections, diseased cells are presented to human Vγ9Vδ2 T cells through an 'inside out' signalling process whereby structurally diverse phosphoantigen (pAg) molecules are sensed by the intracellular domain of butyrophilin BTN3A11-4. Here we show how-in both humans and alpaca-multiple pAgs function as 'molecular glues' to promote heteromeric association between the intracellular domains of BTN3A1 and the structurally similar butyrophilin BTN2A1. X-ray crystallography studies visualized that engagement of BTN3A1 with pAgs forms a composite interface for direct binding to BTN2A1, with various pAg molecules each positioned at the centre of the interface and gluing the butyrophilins with distinct affinities. Our structural insights guided mutagenesis experiments that led to disruption of the intracellular BTN3A1-BTN2A1 association, abolishing pAg-mediated Vγ9Vδ2 T cell activation. Analyses using structure-based molecular-dynamics simulations, 19F-NMR investigations, chimeric receptor engineering and direct measurement of intercellular binding force revealed how pAg-mediated BTN2A1 association drives BTN3A1 intracellular fluctuations outwards in a thermodynamically favourable manner, thereby enabling BTN3A1 to push off from the BTN2A1 ectodomain to initiate T cell receptor-mediated γδ T cell activation. Practically, we harnessed the molecular-glue model for immunotherapeutics design, demonstrating chemical principles for developing both small-molecule activators and inhibitors of human γδ T cell function.


Assuntos
Butirofilinas , Ativação Linfocitária , Fosfoproteínas , Receptores de Antígenos de Linfócitos T gama-delta , Linfócitos T , Animais , Humanos , Antígenos CD/imunologia , Antígenos CD/metabolismo , Butirofilinas/imunologia , Butirofilinas/metabolismo , Camelídeos Americanos/imunologia , Simulação de Dinâmica Molecular , Fosfoproteínas/imunologia , Fosfoproteínas/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Cristalografia por Raios X , Ressonância Magnética Nuclear Biomolecular , Termodinâmica
6.
Materials (Basel) ; 16(13)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37444915

RESUMO

This study conducted plane-strain scaled model tests to investigate the deformation characteristics of geosynthetic reinforced soil (GRS) abutments subjected to vertical loads. Setback distance, i.e., the distance between the back of the abutment facing and the front of the loading plate, was chosen as the investigated influencing factor since it is one of the most frequently used variables by engineers for the design of GRS abutments. This study analyzed the settlements at the top of the abutment, the lateral displacements of the abutment facing, and the volumetric deformations of the abutment under the applied vertical loads. Test results showed that increasing the setback distance could effectively reduce the deformations of the GRS abutment. There existed an optimum setback distance and further increasing the setback distance beyond this optimum value did not have a significant effect on reducing the abutment deformations. The vertical, lateral, and total volumetric deformations of the GRS abutment showed an approximately linear increase with the increase of the applied vertical loads. The lateral volumetric deformations of the GRS abutment were larger than its vertical volumetric deformations and therefore the total volumetric strains of the GRS abutment were not zero based on the test results. However, the theory of zero volume change may still be suitable for the deformation calculation of the GRS abutment since the values of the volumetric strains were minimal. The measured maximum lateral facing displacements were compared with the calculated values using the US Federal Highway Administration (FHWA) method, which assumes zero volume change of the GRS abutment under vertical loads. Comparison results indicated that the FHWA method overestimated the maximum lateral facing displacements of the GRS abutment under vertical loads. An improved method was proposed in this study to calculate the maximum lateral facing displacements under vertical loads based on the theory of zero volume change and a revised distribution of the settlements at the top of the GRS abutment. Results showed that the improved method could better predict the maximum lateral facing displacements as compared to the FHWA method.

7.
J Hazard Mater ; 458: 131836, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37331057

RESUMO

Ochratoxin A (OTA) is among the most prevalent mycotoxins detected in agroproducts, posing serious threats to human and livestock health. Using enzymes to conduct OTA detoxification is an appealing potential strategy. The recently identified amidohydrolase from Stenotrophomonas acidaminiphila, termed ADH3, is the most efficient OTA-detoxifying enzyme reported thus far and can hydrolyze OTA to nontoxic ochratoxin α (OTα) and L-ß-phenylalanine (Phe). To elucidate the catalytic mechanism of ADH3, we solved the single-particle cryo-electron microscopy (cryo-EM) structures of apo-form, Phe- and OTA-bound ADH3 to an overall resolution of 2.5-2.7 Å. The role of OTA-binding residues was investigated by structural, mutagenesis and biochemical analyses. We also rationally engineered ADH3 and obtained variant S88E, whose catalytic activity was elevated by 3.7-fold. Structural analysis of variant S88E indicates that the E88 side chain provides additional hydrogen bond interactions to the OTα moiety. Furthermore, the OTA-hydrolytic activity of variant S88E expressed in Pichia pastoris is comparable to that of Escherichia coli-expressed enzyme, revealing the feasibility of employing the industrial yeast strain to produce ADH3 and its variants for further applications. These results unveil a wealth of information about the catalytic mechanism of ADH3-mediated OTA degradation and provide a blueprint for rational engineering of high-efficiency OTA-detoxifying machineries.


Assuntos
Agroquímicos , Amidoidrolases , Recuperação e Remediação Ambiental , Micotoxinas , Micotoxinas/química , Micotoxinas/toxicidade , Recuperação e Remediação Ambiental/métodos
8.
Int J Food Microbiol ; 387: 110050, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36508953

RESUMO

As a human foodborne pathogen, Listeria monocytogenes can cause severe human listeriosis and develop resistance to antibiotics. Antimicrobial peptides (AMPs) are produced from all kingdoms of life and regarded as promising alternatives to conventional antibiotics. Jelleine-I is an AMP identified from honeybees royal jelly. In this study, we explored the activity and action mechanism of Jelleine-I against L. monocytogenes. We found its minimum inhibitory concentration to be 12.5 µg/mL. Membrane permeability analysis revealed that Jelleine-I increased L. monocytogenes cell membrane permeability, causing calcium leakage. Scanning, transmission electron microscopy and fluorescence microscopy revealed that Jelleine-I destroyed membrane integrity, disrupted intracellular structures and interacted with the bacterial DNA. DNA binding analysis demonstrated that Jelleine-I bound to bacterial genomic DNA. Results of reverse transcription-quantitative PCR revealed that Jelleine-I affected bacterial DNA replication gene expression levels. Moreover, Jelleine-I induced cellular reactive oxygen species (ROS) production from fluorescence intensity analysis, and inhibited bacterial biofilm formation. Results of immunomodulation in Galleria mellonella revealed that Jelleine-I increased host hemocyte counts, upregulated host AMP gene (Gloverin and Cecropin D) expression, and inhibited proinfammatory cytokine (tumor necrosis factor α and interleukin 6) production induced by bacterial infection. It efficiently killed bacteria and increased the survival rate of infected insects to 70 %. Furthermore, Jelleine-I increased the G1 to S phase transition in mammalian cells from cells cycle analysis, and cytotoxicity assay results indicated that it promoted cell proliferation without hemolysis or cytotoxicity. Collectively, Jelleine-I possesses antimicrobial, immunomodulatory and cell proliferative activities, and is a promising candidate for preventing L. monocytogenes emergence and dissemination.


Assuntos
Anti-Infecciosos , Listeria monocytogenes , Listeriose , Animais , Humanos , Peptídeos Antimicrobianos , Listeriose/tratamento farmacológico , Listeriose/microbiologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Mamíferos
9.
Cell Discov ; 8(1): 5, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35075146

RESUMO

KRAS mutation occurs in nearly 30% of human cancers, yet the most prevalent and oncogenic KRAS(G12D) variant still lacks inhibitors. Herein, we designed a series of potent inhibitors that can form a salt bridge with KRAS's Asp12 residue. Our ITC results show that these inhibitors have similar binding affinity with both GDP-bound and GTP-bound KRAS(G12D), and our crystallographic studies reveal the structural basis of inhibitor binding-induced switch-II pocket in KRAS(G12D), experimentally confirming the formation of a salt bridge between the piperazine moiety of the inhibitors and the Asp12 residue of the mutant protein. Among KRAS family proteins and mutants, both ITC and enzymatic assays demonstrate the selectivity of the inhibitors for KRAS(G12D); and the inhibitors disrupt the KRAS-CRAF interaction. We also observed the inhibition of cancer cell proliferation as well as MAPK signaling by a representative inhibitor (TH-Z835). However, since the inhibition was not fully dependent on KRAS mutation status, it is possible that our inhibitors may have off-target effects via targeting non-KRAS small GTPases. Experiments with mouse xenograft models of pancreatic cancer showed that TH-Z835 significantly reduced tumor volume and synergized with an anti-PD-1 antibody. Collectively, our study demonstrates proof-of-concept for a strategy based on salt-bridge and induced-fit pocket formation for KRAS(G12D) targeting, which warrants future medicinal chemistry efforts for optimal efficacy and minimized off-target effects.

10.
Food Microbiol ; 103: 103951, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35082068

RESUMO

This study aimed to investigate the inactivation mechanism of Bacillus cereus spores by slightly acidic electrolyzed water (SAEW). Spore inactivation efficacy of SAEW at different available chlorine concentrations (ACC, 20, 60 and 100 mg/L), as well as spore structures change, coat damage, mutagenesis, and inner membrane (IM) properties were examined. The viability of treated spores with lysozyme addition and spore germination induced by germinant was also examined. The results showed that SAEW could reach maximal 5.81 CFU/mL log reduction with ACC of 100 mg/L for 20 min treatment. Scanning and transmission electron photomicrographs indicated that SAEW treatment rendered spore surface ruptured, IM damage and core contents loss. No mutants were generated in survivors of SAEW treated-spores. SAEW significantly weakened spore viability in high salt medium, losing its ability to retain pyridine-2,6-dicarboxylic acid (DPA) at 85 °C. SAEW-treated spores germinated with l-alanine or inosine induction were mostly stained with propidium iodide (PI) but could not recover via lysozyme addition. Furthermore, SAEW treatment inhibited spore germination in the induction of germinant (mixture of l-alanine and inosine or dodecylamine). These findings indicated that SAEW inactivated spore primarily by damaging the spore IM.


Assuntos
Bacillus cereus , Água , Ácidos , Cloro , Esporos Bacterianos
11.
Artigo em Inglês | MEDLINE | ID: mdl-34768011

RESUMO

Candida albicans can cause local or systemic diseases when host immune status is disrupted. Drug resistance to C. albicans highlights the necessity of novel antifungal drugs. Antimicrobial peptides exhibit potential as antifungal drugs. PAF26 was found to exhibit favorable activity against plant pathogenic fungi. However, it showed low antifungal activity against C. albicans. Here, P255 and P256 with the same composition and different distribution were derived from PAF26. P256 exhibited higher antifungal activity against C. albicans than did P255 and PAF26. P256 and P255 exhibited synergism when combined with amphotericin B (AMB). Both peptides reduced cell wall integrity, rapidly increased membrane permeability, disrupted cell morphology and intracellular alterations. The peptides affected the expression of fungal DNA replication and repair, cell wall synthesis and ergosterol synthesis genes. They increased cellular reactive oxygen species production and bound with fungal genomic DNA. Antibiofilm activities were observed when peptide alone or combined with AMB. Finally, these peptides protected 70% of Galleria mellonella from infection-caused death. Insects treated with peptides exhibited fewer infection foci compared with the untreatment. These results demonstrate the therapeutic potential of the peptides, particularly P256 with clear amphipathicity, in the development of therapies for C. albicans infections.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/fisiologia , DNA , Interações Hospedeiro-Patógeno , Larva/efeitos dos fármacos , Larva/microbiologia , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Mariposas , Peptídeos/química , Ligação Proteica , Conformação Proteica , Espécies Reativas de Oxigênio
12.
Front Plant Sci ; 13: 1096619, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36714695

RESUMO

As a leaf homologous organ, soybean pods are an essential factor in determining yield and quality of the grain. In this study, a recognition method of soybean pods and estimation of pods weight per plant were proposed based on improved YOLOv5 model. First, the YOLOv5 model was improved by using the coordinate attention (CA) module and the regression loss function of boundary box to detect and accurately count the pod targets on the living plants. Then, the prediction model was established to reliably estimate the yield of the whole soybean plant based on back propagation (BP) neural network with the topological structure of 5-120-1. Finally, compared with the traditional YOLOv5 model, the calculation and parameters of the proposed model were reduced by 17% and 7.6%, respectively. The results showed that the average precision (AP) value of the improved YOLOv5 model reached 91.7% with detection rate of 24.39 frames per millisecond. The mean square error (MSE) of the estimation for single pod weight was 0.00865, and the average coefficients of determination R2 between predicted and actual weight of a single pod was 0.945. The mean relative error (MRE) of the total weight estimation for all potted soybean plant was 0.122. The proposed method can provide technical support for not only the research and development of the pod's real-time detection system, but also the intelligent breeding and yield estimation.

13.
Int J Biol Macromol ; 109: 1302-1310, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29175162

RESUMO

Pullulanase with high catalytic efficiency has attracted great attention from both the academic and industrial communities for its wide application in cold starch hydrolysis. A novel pullulanase gene pul703 was cloned from a mesophilic bacteria Bacillus pseudofirmus 703. Pul703 was characterized to be a type I pullulanase with maximal activity at 45°C and good low-temperature stability, more than 70% of activity was detected after incubation at 25-35°C for 72h. Pul703 obtained the maximal activity around pH 7.0-8.0, and was highly active and stable over a wide pH range of 5.5-9.5, more than 80% of activity was retained after 12h incubation in these pHs. Pul703 was EDTA-resistant and detergent-tolerant, with a relative activity of 100, 99, and 114.8% at the presence of 10mM EDTA, 10% of Triton X-100 and Tween 20, respectively. Pul703 can efficiently hydrolyze pullulan with a specific activity of 270U/mg, which was higher than all reported type I pullulanases. In addition, Pul703 can act synergistically with α-amylase BLA to efficiently hydrolyze amylopectin. These results suggested that Pul703 was a good candidate for cold starch hydrolysis.


Assuntos
Bacillus/enzimologia , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/metabolismo , Concentração de Íons de Hidrogênio , Bacillus/genética , Catálise , Quelantes/química , Quelantes/farmacologia , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Sequência Conservada , Detergentes/química , Detergentes/farmacologia , Ativação Enzimática , Expressão Gênica , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/isolamento & purificação , Hidrólise , Cinética , Mutação , Proteínas Recombinantes , Análise de Sequência de DNA , Especificidade por Substrato , Temperatura
14.
Zhen Ci Yan Jiu ; 42(2): 102-6, 2017 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-29071955

RESUMO

OBJECTIVE: To explore the potential mechanism of acupuncture stimulation of "Taichong" (LR 3) and "Neiguan" (PC 6) in spontaneous hypertension rats (SHR) by investigating its effects on blood pressure and contents of aspartic acid(Asp) and glutamic acid (Glu) in the rostral ventrolateral medulla (RVLM) region. METHODS: A total of 75 SHR were randomized into model group, Taichong (LR 3) group, Neiguan (PC 6) group, LR 3+non-acupoint group and LR 3 + PC 6 group (n=15 rats in each group), and 15 Wistar rats of the same age were used as the normal control group. The filiform needles were inserted into the abovementioned acupoints and non-acupoint, twirled for a while and then retained for 30 min. The treatment was conducted once per day, 15 times in total. The rats' tail blood pressure was examined on day 1, 3, 7 and 15 after acupuncture treatment by using a non-invasive blood pressure monitor. At the end of experiment, the contents of Asp and Glu in the RVLM were detected by high-performance liquid chromatography with UV technique. RESULTS: On day 1, 3, 7 and 15 after the acupuncture treatment, the raised systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) of PC 6, LR 3, LR 3 + non-acupoint and LR 3 + PC 6 groups were all decreased significantly compared with the model group (P<0.05). On day 15, the effect of the LR 3 + PC 6 group was significantly superior to that of the LR 3, PC 6, and LR 3 + non-acupoint groups in reducing the levels of SBP, DBP, and MBP (P<0.05).Compared with the normal control group, the contents of Asp and Glu in RVLM were significantly higher in the model group (P<0.05). After acupuncture intervention, both Asp and Glu levels in the PC 6, LR 3, LR 3 + non-acupoint, and LR 3 + PC 6 groups were markedly lower in comparison with the model group (P<0.05), and those of the LR 3 + PC 6 group were notably lower than those in the LR 3 and PC 6 groups (P<0.05). CONCLUSIONS: Acupuncture stimulation of PC 6, LR 3, LR 3 + non-acupoint and LR 3 + PC 6 (in particular) is effective in lowering blood pressure in spontaneous hypertension rats, which may be associated with its effects in lowering Asp and Glu contents in RVLM.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Ácido Aspártico/metabolismo , Ácido Glutâmico/metabolismo , Hipertensão/terapia , Bulbo/metabolismo , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Wistar
15.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(5): 1331-4, 2015 May.
Artigo em Chinês | MEDLINE | ID: mdl-26415455

RESUMO

Chaenomeles speciosa fruits were extracted using water. The extracts were precipitated with 20%~95% (φ) ethanol, respectively. The amount of total polysaccharide was measured with phenol-sulfuric acid method. A method using high-performance size-exclusion chromatography (HPSEC) equipped with multiangle laser-light-scattering photometry (MALLS) and differential refractometry (RI) was presented for determining the molecular weight and molecular weigh distribution. RAW264.7 macrophage were cultured and stimulated with the polysaccharides in vitro and the production of nitric oxide in the cells was determined by the Griess assay. The aim of the study is to determine the amount and the molecular weight of the polysaccharides from Chaenomeles speciosa fruits, and preliminary investigate the immunomodulatory activity, The study provided the basis datas for the further research of Chaenomeles speciosa fruits. , and provided a simple and system method for the research of natural polysaccharide. The ethanol fractional precipitation showed that the order of total polysaccharide content was 95%>80%>40% ≥60%>20%. The results indicated that most polysaccharide from Chaenomeles speciosa fruits might be precipitated when ethanol concentration was up to 95% (T) and the crude polysaccharide purity had risen from 35. 1% to 45. 0% when the concentration of ethanol increased from 20% to 95%. HPSEC-MALLS-RI system showed that all the polysaccharide samples had the similar compositions. They appeared three chromatographic peaks and the retention time were not apparently different. The Mw were 6. 570 X 10(4) g . mol-1 and 1. 393 X 10(4) g . mol-1 respectively, and one less than 10 000 which was failure to obtain accurate values. The molecular weight of the first two polysaccharide distribution index(Mw/Mn)were 1. 336 and 1. 639 respectively. The polysaccharide samples had not exhibited immunomodulatory activity assessed on the basis of nitric oxide production by RAW264. 7 macrophage cells in the experiment.


Assuntos
Frutas/química , Polissacarídeos/química , Rosaceae/química , Animais , Linhagem Celular , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Etanol , Precipitação Fracionada , Macrófagos/efeitos dos fármacos , Camundongos , Peso Molecular , Óxido Nítrico/química , Refratometria , Ácidos Sulfúricos , Água
16.
Inorg Chem ; 53(10): 5029-36, 2014 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-24801637

RESUMO

Two enantiotopic 1D chain compounds, [Cu3(L1)3(H2O)2(H2W12O40)]·4H2O (1a,b; L1 = 2-(4,6-bis(pyridin-2-yl)pyridin-2-yl)pyridine), crystallizing in the chiral space group P212121 were prepared and spontaneously resolved in the absence of any chiral source. Interestingly, compounds 1a,b can be prepared from a [W7O24](6-) aqueous solution, [(n-C4H9)4N]4[W10O32], or Na10[H2W12O42], but when [H2W12O40](6-) aqueous solution was the starting material, the achiral compound [CuL1]2[H4W12O40]·5H2O (2) was obtained. When a terpyridine ligand (L2) having a coordination mode similar to that of L1 was used, the mesomeric dimer [Cu3(L2)3(H2O)(H2W12O40)]2·4H2O (3) was obtained from [W7O24](6-) aqueous solution or Na10[H2W12O42], but from [H2W12O40](6-) aqueous solution only compound [Cu2(L2)2Cl2]2[W10O32] (4) was isolated. It is notable that in compounds 1a,b and 3 the symmetry of the α-[H2W12O40](6-) cluster is broken by asymmetric coordination with metal-organic units in a similar mode. As the asymmetric subunit based on a tridecorated [H2W12O40](6-) cluster can be obtained from several isopolyoxotungstate sources except for [H2W12O40](6-), we speculate that the symmetry breaking of α-[H2W12O40](6-) depends on the transformation of isopolyoxotungstates. Furthermore, during the transformation a possible reaction intermediate as the precursor for 1a,b, compound [Cu3(L1)3(H2O)3(H4W11O38)] (5), has been presented and characterized by density functional theory (DFT) calculations.


Assuntos
Cobre/química , Compostos Organometálicos/química , Compostos de Tungstênio/química , Cristalografia por Raios X , Modelos Moleculares , Compostos Organometálicos/síntese química , Teoria Quântica
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