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1.
Nature ; 606(7915): 694-699, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35732762

RESUMEN

The realization of controllable fermionic quantum systems via quantum simulation is instrumental for exploring many of the most intriguing effects in condensed-matter physics1-3. Semiconductor quantum dots are particularly promising for quantum simulation as they can be engineered to achieve strong quantum correlations. However, although simulation of the Fermi-Hubbard model4 and Nagaoka ferromagnetism5 have been reported before, the simplest one-dimensional model of strongly correlated topological matter, the many-body Su-Schrieffer-Heeger (SSH) model6-11, has so far remained elusive-mostly owing to the challenge of precisely engineering long-range interactions between electrons to reproduce the chosen Hamiltonian. Here we show that for precision-placed atoms in silicon with strong Coulomb confinement, we can engineer a minimum of six all-epitaxial in-plane gates to tune the energy levels across a linear array of ten quantum dots to realize both the trivial and the topological phases of the many-body SSH model. The strong on-site energies (about 25 millielectronvolts) and the ability to engineer gates with subnanometre precision in a unique staggered design allow us to tune the ratio between intercell and intracell electron transport to observe clear signatures of a topological phase with two conductance peaks at quarter-filling, compared with the ten conductance peaks of the trivial phase. The demonstration of the SSH model in a fermionic system isomorphic to qubits showcases our highly controllable quantum system and its usefulness for future simulations of strongly interacting electrons.

2.
Clin Radiol ; 78(10): e707-e717, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37407367

RESUMEN

AIM: To predict progression within 6 months after chimeric antigen receptor-modified (CAR) T-cell therapy for relapsed/refractory (R/R) B-cell non-Hodgkin's lymphoma (B-NHL) patients by radiomic indexes derived from contrast-enhanced computed tomography (CECT) examinations. MATERIALS AND METHODS: Seventy R/R B-NHL patients who underwent CECT before treatment with CAR T-cells were examined retrospectively. In total, 297 volumes of interest for lesions were segmented from CECT images. Patients without and with disease progression were assigned to groups 1 and 2, respectively. Radiomic and combined predictive models were constructed by three machine-learning algorithms using features from the training set, respectively. Furthermore, predictive models were constructed based on multi-lesion-based and largest-lesion-based radiomic features, respectively. RESULTS: In the test set, no marked differences were observed between the areas under the curves (AUCs) of the combined and radiomic models for all three machine-learning algorithms (all p>0.05). Differences in machine-learning algorithms did not significantly affect the predictive performances of the models. Radiomics and combined models constructed with multi-lesion-based radiomic features showed better predictive performances than those applying largest-lesion-based radiomic features (all p<0.05 for comparisons between combined models). CONCLUSION: CECT-based radiomic features may be applied to predict disease progression in R/R B-NHL patients within 6 months after CAR T-cell treatment, and radiomic features from multiple lesions may have better predictive efficacy. Different machine-learning algorithms may not show significant differences in prediction performance.


Asunto(s)
Linfoma no Hodgkin , Receptores Quiméricos de Antígenos , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Progresión de la Enfermedad , Tratamiento Basado en Trasplante de Células y Tejidos
3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(6): 1094-1098, 2021 Dec 18.
Artículo en Zh | MEDLINE | ID: mdl-34916688

RESUMEN

OBJECTIVE: To assess the activation function of specific tumor polypeptide for dendritic cell vaccine on lymphocytes proliferation, production of cytokines and killing activity in vitro by using dendritic cells as antigen presenting vector. METHODS: Peripheral blood dendritic cells (DC) and cytokine-induced killer (CIK) were isolated and cultured by adherent culture method; CCK-8 method was used to assess the proliferation function of lymphocytes and the killing function of lymphocytes to tumor cells; enzyme-linked immunospot assay method was used to evaluate the secretion function of cytokines. The experiment was divided into tumor polypeptide group (peptide with DC-CIK), DC-CIK group and CIK group. RESULTS: With presence of interleukin-2 (IL-2) in the culture system, the lymphocyte proliferation of the three groups was obvious. The absorbance at 450 nm of tumor polypeptide group was significantly higher than that of CIK group at the time points day 4 and day 6 (day 4: Z=-3.79, P < 0.001; day 6: Z =-2.95, P < 0.01). The absorbance at 450 nm of group tumor polypeptide was significantly higher than that of DC-CIK group on day 4 (Z=-2.02, P < 0.05). Without IL-2 in the culture system, lymphocytes proliferated slowly in all the three groups, and there was no significant difference in 450 nm absorbance at each time point. The levels of IL-4 (Z=-2.61, P < 0.01), granulocyte-macrophage colony-stimulation factor (GM-CSF, Z=-3.85, P < 0.001), interferon- γ (IFN- γ, Z=-3.56, P < 0.001) and tumor necrosis factor-α (TNF-ɑ, Z=-3.40, P < 0.001) of tumor polypeptide group were higher than those of CIK group. There was no significant difference in the production of cytokines except IL-4 (Z=-2.15, P < 0.05) when tumor polypeptide group was compared with DC-CIK group. The production of IFN-γ (Z=-2.44, P < 0.05), TNF-ɑ (Z=-2.26, P < 0.05) and GM-CSF (Z=-3.73, P < 0.001) in DC-CIK group were higher than those of CIK group. Although there was no significant difference in killing activity between tumor polypeptide group, DC-CIK group and CIK group at hour 18 and hour 24, and the killing activity of tumor polypeptide group was higher than that of the other two groups. CONCLUSION: Tumor peptide combined with dendritic cells can improve the proliferation activity of CIK cells in vitro, and increase the secretion of several cytokines.


Asunto(s)
Células Dendríticas , Péptidos
4.
Zhonghua Wai Ke Za Zhi ; 59(10): 842-847, 2021 Oct 01.
Artículo en Zh | MEDLINE | ID: mdl-34619910

RESUMEN

Objective: To explore the feasibility and clinical value of a new classification for resectable intrahepatic cholangiocarcinoma (IHCC) according to the actual anatomy. Methods: The data of 135 patients with IHCC who were admitted to the Department of Hepatopancreatobiliary Surgery,Second Affiliated Hospital of Zhejiang University School of Medicine from November 2011 to November 2020 after discussion by a multidisciplinary team and planned to undergo radical resection were analyzed retrospectively. There were 77 males and 58 females,with a median age of 61 years (range:26 to 86 years),of which 38 cases had vascular invasion. This new classification was carried out independently by two hepatobiliary surgeons. First,a preliminary classification was made based on the location of the tumor,and then the final classification was based on vascular invasion. All patients were followed up by telephone,and the follow-up was as of November 2020. Survival time is defined as the time after surgery to follow-up or death. Log-rank test was used to compare patients' median recurrence-free survival and overall survival time. The Cox proportional hazard model was used to analyze the prognosis factors of the overall survival time of patients with IHCC. Results: Among the 135 patients,129 underwent R0 resection and 6 underwent R1 resection. According to the actual anatomy,28 cases (20.7%) belonged to segmental type, 43 cases (31.9%) belonged to branch type, 64 cases (47.4%). The median survival time of all patients was 35.2 months(95%CI:21.3 to 70.5 months),the 1-year cumulative survival rate was 75.1%,the 3-year cumulative survival rate was 45.8%,and the 5-year cumulative survival rate was 39.0%. After grouping according to the classification,the median survival time of segmental patients was 36.9 months (more than 50% of patients reached the median survival time),and the median survival time of branched patients was 33.8 months (95%CI:16.8 to 38.5);The median survival time of lobe patients was 25.0 months (95%CI:13.6 to 58.7). The result of Log-rank test between groups indicated that the median survival time of patients with segmental type was better than that of patients with branch and lobe type(HR=2.03,95%CI:1.24 to 3.64,P=0.006);There was no significant difference in survival time between patients with branch type and lobe type (P=0.685). The results of the multivariate analysis of the Cox risk ratio model suggested that the actual anatomical location classification (HR=2.32,95%CI:1.10 to 4.92,P=0.028) and the postoperative lymph node metastasis rate (HR=2.06,95%CI:1.24 to 3.45,P=0.005) were independent factors related to survival after radical resection of IHCC patients. Conclusion: It is simple and convenient to classify resectable IHCC by actual anatomy,which can be used to preliminarily judge the prognosis of patients and provide a feasible classification scheme for the clinic.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos , Colangiocarcinoma/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
5.
Int J Med Sci ; 17(12): 1673-1682, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32714070

RESUMEN

Objective: Type 2 diabetes mellitus (T2DM) is a chronic condition resulting from insulin resistance and insufficient ß-cell secretion, leading to improper glycaemic regulation. Previous studies have found that excessive fat deposits in organs such as the liver and muscle can cause insulin resistance through lipotoxicity that affects ß-cell function. The relationships between fat deposits in pancreatic tissue, the function of ß-cells, the method of visceral fat evaluation and T2DM have been sought by researchers. This study aims to elucidate the role of pancreatic fat deposits in the development of T2DM using quantitative computed tomography (QCT), especially their effects on islet ß-cell function. Methods: We examined 106 subjects at the onset of T2DM who had undergone abdominal QCT. Estimated pancreatic fat and liver fat were quantified using QCT and calculated. We analysed the correlations with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores and other oral glucose tolerance test-derived parameters that reflect islet function. Furthermore, correlations of estimated pancreatic fat and liver fat with the area under the curve for insulin (AUCINS) and HOMA-IR were assessed with partial correlation analysis and demonstrated by scatter plots. Results: Associations were found between estimated liver fat and HOMA-IR, AUCINS, the modified ß-cell function index (MBCI) and Homeostatic Model Assessment ß (HOMA-ß). However, no significant differences existed between estimated pancreas fat and those parameters. Similarly, after adjustment for sex, age and body mass index, only estimated liver fat was correlated with HOMA-IR and AUCINS. Conclusions: This study suggests no significant correlation between pancreatic fat deposition and ß-cell dysfunction in the early stages of T2DM using QCT as a screening tool. The deposits of fat in the pancreas and the resulting lipotoxicity may play an important role in the late stage of islet cell function dysfunction as the course of T2DM progresses.


Asunto(s)
Tejido Adiposo/diagnóstico por imagen , Diabetes Mellitus Tipo 2/diagnóstico , Células Secretoras de Insulina/patología , Páncreas/diagnóstico por imagen , Tejido Adiposo/patología , Adulto , Glucemia/genética , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/metabolismo , Resistencia a la Insulina/genética , Células Secretoras de Insulina/metabolismo , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/metabolismo , Hígado/metabolismo , Hígado/patología , Masculino , Persona de Mediana Edad , Páncreas/patología , Tomografía Computarizada de Emisión
6.
Zhonghua Fu Chan Ke Za Zhi ; 55(10): 667-672, 2020 Oct 25.
Artículo en Zh | MEDLINE | ID: mdl-33120477

RESUMEN

Objective: To investigate and analyze disease status and risk factors of venous thromboembolism (VTE) during pregnancy and puerperium in our country. Methods: Clinical datas were collected from 575 patients diagnosed with VTE during pregnancy and puerperium and hospitalized in nine medical institutions in our country from January 1, 2015 to November 30, 2019, and retrospectively analyzed it's disease status and risk factors. Results: (1) The proportion of VTE in pregnancy and puerperium was 50.6% (291/575) and 49.4% (284/575), respectively. Four patients died, the mortality rate was 0.7% (4/575). The cause of death was pulmonary embolism. (2) The location of VTE during pregnancy and puerperium was mainly in the lower limb vascular (76.2%, 438/575), followed by pulmonary vessels (7.1%, 41/575). (3) In the risk factors of VTE, cesarean section accounted for 32.3% (186/575), maternal advance age accounted for 27.7% (159/575), braking or hospitalization during pregnancy accounted for 13.6% (78/575), other risk factors accounted for more than 5% were previous VTE, obesity, preterm birth, assistant reproductive technology conception and so on, pre-eclampsia and multiple pregnancy accounted for 4.9% (28/575) respectively. In addition, some patients with VTE did not have any of the above risk factors, and the incidence rate was as high as 23.1% (133/575). Conclusions: The occurrence of VTE during pregnancy and puerperium is related to multiple risk factors, and could lead to matemal death, It is very necessary to screen VTE risk factors for all pregnant women, to make corresponding prevention and control measures.


Asunto(s)
Complicaciones Cardiovasculares del Embarazo/epidemiología , Tromboembolia Venosa/epidemiología , Adulto , Cesárea , China/epidemiología , Femenino , Humanos , Recién Nacido , Embarazo , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Tromboembolia Venosa/etiología
7.
Zhonghua Yi Xue Za Zhi ; 99(34): 2670-2674, 2019 Sep 10.
Artículo en Zh | MEDLINE | ID: mdl-31505717

RESUMEN

Objective: To investigate the expression and interaction of VHL/HIF-α pathways including HIF-1α, HIF-2α as well as VHL in erythroid progenitor cells of bone marrow from chronic mountain sickness (CMS) patients. Methods: A total of 25 patients with CMS and 21 healthy controls were recruited for this study. The CD71(+)CD235a(+) cells in bone marrow mononuclear cells, marked as erythroid progenitor cells, were isolated using MACS separation technology. The expression levels of HIF-1α, HIF-2α and VHL in erythroid progenitor cells were detected by Western blotting and real-time fluorescence quantitative PCR. Results: The mRNA levels of HIF-2α were higher in erythroid progenitor cells of CMS than in healthy controls [1.68 (0.81, 2.22) vs 0.98 (0.60, 1.19), P<0.05], while HIF-1α and VHL mRNA levels were similar between the two groups (P>0.05). Spearman analyses indicated that HIF-2α mRNA was positively associated with hemoglobin (Hb) levels in the erythroid progenitor cells of CMS (ρ=0.504, P<0.05). Furthermore, the mRNA level of HIF-2α was correlated with the mRNA level of VHL in the erythroid progenitor cells of CMS (ρ=0.647, P<0.05).The protein levels of HIF-2α in the erythroid progenitor cells of CMS were higher than that of healthy controls [0.94(0.68, 3.30) vs 0.59(0.30, 0.88), P<0.05], but the protein levels of HIF-1α and VHL were similar between the two groups (P>0.05). Conclusions: The abnormal increased expression of HIF-2α in the erythroid progenitor cells of CMS patients leads to the abnormal expression of hypoxia sensitive genes downstream, participating in the occurrence and development of CMS.


Asunto(s)
Mal de Altura , Transducción de Señal , Células Precursoras Eritroides , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau
8.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(5): 381-387, 2019 May 24.
Artículo en Zh | MEDLINE | ID: mdl-31142082

RESUMEN

Objective: To explore the characteristics of postural blood pressure changes in elderly inpatients and the related factors of orthostatic hypotension (OH). Methods: This study was a clinical case control study. Two hundred and sixty-six elderly patients (≥60 years old), who were hospitalized between April 2016 and November 2017 in Geriatric Department of Peking University First Hospital, were included. They were divided into direct standing group and indirect standing group. Direct standing group involved 102 patients, they changed posture from supine directly to standing position, and the blood pressures at the moments of supine, immediately after standing and the first, second, and third minute after standing were recorded by continuous noninvasive arterial pressure (CNAP) system. Indirect standing group involved 164 patients, and they changed posture from supine to sitting for 3 minutes, and then changed to standing position. Blood pressures at the moments of supine, immediately after sitting, the third minute after sitting, immediately after standing and the third minute after standing was recorded by CNAP. Blood pressure changes after different postural changes mode and the rates of OH were compared. The related factors of OH was analyzed by binary logistic regression analysis. Results: The lowest systolic blood pressures (SBP) mostly occurred immediately after postural change: immediately after standing for direct standing group (86.3%(88/102)), and immediately after sitting for indirect standing group (59.1%(97/164)). The lowest diastolic blood pressures (DBP) mostly occurred immediately after standing in the two groups: 87.3%(89/102) for direct standing group and 43.3% (71/164) for indirect standing group. The maximum SBP drop (SBP of supine minus the lowest SBP during postural changes) of direct standing group was significantly higher than indirect standing group (median 20.5(14.0, 29.3) vs. 18.0(11.0, 26.0) mmHg (1 mmHg=0.133 kPa, P<0.05). The rates of OH occurred immediately and within 3 minutes from supine to standing position were significantly higher in direct standing group than in indirect standing group (65.7% (67/102) vs. 43.9% (72/164), and 70.6% (72/102) vs. 49.4% (81/164), both P<0.05). Binary logistic regression analysis showed that brachial-ankle pulse wave velocity was positively associated with OH after a transition from supine to standing position (immediately and within 3 minutes, OR=1.002 (95%CI 1.000-1.004), 1.003 (95%CI 1.001-1.006), P=0.014, 0.006) in direct standing group. Conclusions: OH is common in elderly hospitalized patients. The most obvious blood pressure changes are likely to occur immediately after position changes. Adding a sitting position during the transition of supine to standing position may decrease the amplitude of SBP drop. Brachial-ankle pulse wave velocity is associated with OH after the transition from the supine to standing position in the elderly inpatients.


Asunto(s)
Presión Arterial , Hipotensión Ortostática , Anciano , Índice Tobillo Braquial , Presión Sanguínea , Determinación de la Presión Sanguínea , Estudios de Casos y Controles , Humanos , Hipotensión Ortostática/diagnóstico , Persona de Mediana Edad , Postura , Análisis de la Onda del Pulso
9.
Artículo en Zh | MEDLINE | ID: mdl-31495106

RESUMEN

Objective: To study the effect of particulate matter 2.5 (PM(2.5)) on oncogene expression in human bronchial epithelial (HBE) cells. Methods: HBE cells were selected as the study subjects, and PM(2.5) treatment group (10 µg/ml and 50 µg/ml) , negative control group and positive control group (10 µmol/L Cr(6+)) were set. CCK8 assay was used to test the IC(50) value of PM(2.5). HBE cells were treated with PM(2.5) for 24 h at 10 µg/ml and 50 µg/ml, additionally, cells were treated with blank as negative control, 10 µmol/L Cr(6+) as a positive control for 24 h. After the treatment, mRNA expression of oncogenes including c-myc, c-fos, k-ras and p53 were detected by fluorescent quantitative RT-PCR, the protein expression of oncogenes were detected with western blot. Results: The IC(50) value of PM(2.5) in HBE cells is 70.12 µg/ml. The qRT-PCR data showed that compared with the control group, the expression level of c-myc gene increased by respectively 500.1%、780.7%、305.3% after exposure to 10、50 µg/ml PM(2.5) and positive control group; c-fos gene increased respectively 34.0%、76.7%、131.3% after exposure to 10、50 µg/ml PM(2.5) and positive control group; k-ras gene increased respectively 50.3%、107.0%、49.7% after exposure to 10、50 µg/ml PM(2.5) and positive control group; p53 gene decreased by 28.3%、28.7%、59.7% after exposure to 10、50 µg/ml PM(2.5) and positive control group. The western blot results showed that compared with the control group, c-myc protein increased respectively 29.7%、77.3% after exposure to 50 µg/ml PM(2.5) and positive control group; c-fos protein increased respectively 200.3%、137.0% after exposure to 50 µg/ml PM(2.5) and positive control group; k-ras protein increased respectively 106.3%、130.3%、116.7% after exposure to 10、50 µg/ml PM(2.5) and positive control group; p53 protein decreased by 43.7%、53.3%、52.1% after exposure to 10、50 µg/ml PM(2.5) and positive control group. Conclusion: PM(2.5) could promote the expression of oncogenes in HBE cells, the carcinogenicity of haze might be related to promotion of oncogenes expression induced by PM(2.5).


Asunto(s)
Células Epiteliales/efectos de los fármacos , Oncogenes , Material Particulado/toxicidad , Bronquios/citología , Células Cultivadas , Humanos , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína p53 Supresora de Tumor/genética
10.
Zhonghua Yi Xue Za Zhi ; 98(14): 1088-1092, 2018 Apr 10.
Artículo en Zh | MEDLINE | ID: mdl-29690721

RESUMEN

Objective: This study was aimed at investigating the levels and relationships of vascular endothelial growth factor (VEGF) and its receptor(VEGFR) in the bone marrow mononuclear cells (MNC) of chronic mountain sickness (CMS). Methods: A total of 34 patients with CMS and 30 controls residing at altitudes of 3 000-4 500 m were recruited for this study. The levels of VEGF, VEGFR1 and VEGFR2 in bone marrow MNC were detected by flow cytometry technique and RT-qPCR. Results: The percentage of VEGFR2 positive cells in the bone marrow MNC of CMS were higher than that of the controls[20.7% (8.1%, 67.6%) vs 8.1% (2.2%, 14.9%), P<0.05], but that of VEGFR1-positive and VEGF-positive were similar in CMS and controls. The mRNA levels of VEGFR2 were higher in the bone marrow MNC of CMS than in the controls[1.7(1.0, 5.1) vs 1.0(0.4, 2.7), P<0.05], while VEGF and VEGFR1 mRNA levels were similar between the two groups. The percentage of VEGFR2 positive cells in CMS were significantly correlated with hemoglobin (r=0.453, P=0.007) and the percentage of VEGF-positive cells (r=0.373, P=0.030). Conclusions: Bone marrow MNC of CMS may show enhanced activity of the VEGF-VEGFR2 pathway, and it appears to be involved in the pathogenesis of CMS.


Asunto(s)
Mal de Altura/metabolismo , Células de la Médula Ósea/metabolismo , Factor A de Crecimiento Endotelial Vascular/fisiología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Altitud , Médula Ósea , Enfermedad Crónica , Humanos , ARN Mensajero , Transducción de Señal
12.
Oral Dis ; 22(5): 391-8, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26855200

RESUMEN

OBJECTIVE: Candida-induced denture stomatitis is a common debilitating problem among denture wearers. Previously, we described the fabrication of a new denture material that released antifungal drugs when immersed in phosphate buffered saline. Here, we use more clinically relevant immersion conditions (human saliva; 37°C) and measure miconazole release and bioactivity. MATERIALS AND METHODS: Disks were prepared by grafting PNVP [poly(N-vinyl-2-pyrrolidinone)] onto PMMA [poly(methylmethacrylate)] using plasma initiation (PMMA-g-PNVP) and then loaded with miconazole. Drug-loaded disks were immersed in 10-100% human saliva (1-30 days). Miconazole release was measured and then tested for bioactivity vs miconazole-sensitive and miconazole-resistant Candida isolates. RESULTS: HPLC was used to quantify miconazole levels in saliva. Miconazole-loaded disks released antifungal drug for up to 30 days. Higher drug release was found with higher concentrations of saliva, and, interestingly, miconazole solubility was increased with higher saliva concentrations. The released miconazole retained its anticandidal activity. After immersion, the residual miconazole could be quenched and the disks recharged. Freshly recharged disks displayed the same release kinetics and bioactivity as the original disks. Quenched disks could also be charged with chlorhexidine that displayed anticandidal activity. CONCLUSIONS: These results suggest that PMMA-g-PNVP is a promising new denture material for long-term management of denture stomatitis.


Asunto(s)
Antifúngicos/administración & dosificación , Candida/efectos de los fármacos , Materiales Dentales/química , Dentaduras , Saliva/efectos de los fármacos , Adulto , Antifúngicos/química , Antifúngicos/farmacocinética , Candida/aislamiento & purificación , Clorhexidina/análogos & derivados , Clorhexidina/farmacología , Preparaciones de Acción Retardada , Materiales Dentales/farmacocinética , Relación Dosis-Respuesta a Droga , Portadores de Fármacos , Femenino , Gentamicinas/administración & dosificación , Gentamicinas/química , Gentamicinas/farmacocinética , Humanos , Masculino , Metilmetacrilatos/administración & dosificación , Metilmetacrilatos/química , Metilmetacrilatos/farmacocinética , Miconazol/administración & dosificación , Miconazol/química , Miconazol/farmacocinética , Persona de Mediana Edad , Polimetil Metacrilato/administración & dosificación , Polimetil Metacrilato/química , Polimetil Metacrilato/farmacocinética , Pirrolidinonas/administración & dosificación , Pirrolidinonas/química , Pirrolidinonas/farmacocinética
13.
Genet Mol Res ; 15(1)2016 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-27050954

RESUMEN

Lipase-producing bacteria are naturally-occurring, industrially-relevant microorganisms that produce lipases, which can be used to synthesize biodiesel from waste oils. The efficiency of lipase expression varies between various microbial strains. Therefore, strains that can produce lipases with high efficiency must be screened, and the conditions of lipase metabolism and optimization of the production process in a given environment must be thoroughly studied. A high efficiency lipase-producing strain was isolated from the sediments of Jinsha River, identified by 16S rRNA sequence analysis as Serratia marcescens, and designated as HS-L5. A schematic diagram of the genome sequence was constructed by high-throughput genome sequencing. A series of genes related to lipid degradation were identified by functional gene annotation through sequence homology analysis. A genome-scale metabolic model of HS-ML5 was constructed using systems biology techniques. The model consisted of 1722 genes and 1567 metabolic reactions. The topological graph of the genome-scale metabolic model was compared to that of conventional metabolic pathways using a visualization software and KEGG database. The basic components and boundaries of the tributyrin degradation subnetwork were determined, and its flux balance analyzed using Matlab and COBRA Toolbox to simulate the effects of different conditions on the catalytic efficiency of lipases produced by HS-ML5. We proved that the catalytic activity of microbial lipases was closely related to the carbon metabolic pathway. As production and catalytic efficiency of lipases varied greatly with the environment, the catalytic efficiency and environmental adaptability of microbial lipases can be improved by proper control of the production conditions.


Asunto(s)
Proteínas Bacterianas/metabolismo , Genoma Bacteriano/genética , Lipasa/metabolismo , Biología de Sistemas/métodos
14.
Mol Biol (Mosk) ; 50(2): 368-75, 2016.
Artículo en Ruso | MEDLINE | ID: mdl-27239859

RESUMEN

Cytochrome P450nor catalyzes an unusual reaction that transfers electrons from NADP/NADPH to bound heme directly. To improve the expression level of P450nor2 from Cylindrocarpon tonkinense (C.P450nor2), Escherichia coli system was utilized to substitute the yeast system we constructed for expression of the P450nor2 gene, and the protein was purified in soluble form using Ni(+)-NTA affinity chromatography. In contrast to P450nor from Fusarium oxysporum (F.P450nor) and P450nor1 from Cylindrocarpon tonkinense (C.P450nor1), C.P450nor2 shows a dual specificity for using NADH or NADPH as electron donors. The present study developed a computational approach in order to illustrate the coenzyme specificity of C.P450nor2 for NADH and NADPH. This study involved homology modeling of C.P450nor2 and docking analyses of NADH and NADPH into the crystal structure of F.P450nor and the predictive model of C.P450nor2, respectively. The results suggested that C.P450nor2 and F.P450nor have different coenzyme specificity for NADH and NADPH; whilst the space around the B'-helix of the C.P450nor2, especially the Ser79 and Gly81, play a crucial role for the specificity of C.P450nor2. In the absence of the experimental structure of C.P450nor2, we hope that our model will be useful to provide rational explanation on coenzyme specificity of C.P450nor2.


Asunto(s)
Sistema Enzimático del Citocromo P-450/química , Fusarium/enzimología , Simulación del Acoplamiento Molecular , Catálisis , Coenzimas , Sistema Enzimático del Citocromo P-450/biosíntesis , Sistema Enzimático del Citocromo P-450/genética , Cinética , NADP/química
15.
Zhonghua Fu Chan Ke Za Zhi ; 51(3): 204-8, 2016 Mar.
Artículo en Zh | MEDLINE | ID: mdl-27030500

RESUMEN

OBJECTIVE: To determine the effects of adiponectin on high glucose induced BeWo cell proliferation in vitro. METHODS: BeWo cells were seeded in 96-well plates at the appropriate density. After treatments with high glucose (25 mmol/L), western blot analysis of cyclin D1 and a colorimetric assay (cell counting kit-8, CCK-8) were used to analyse BeWo cells' proliferation, and western blot was used to detect the expression of adiponectin. Moreover, we added adiponectin (20 µg/ml) in the culture medium and three methods were utilized for cell proliferation analysis: CCK-8, cell cycle analysis (by flow cytometry) and proliferating cell nuclear antigen (PCNA) immunocytochemical staining. RESULTS: Compared to BeWo cells cultured by normal glucose and high mannitol, the proliferation of BeWo cells treated by high glucose increased (P<0.05). Compared with BeWo cells cultured by high mannitol, the expression of adiponectin in BeWo cells treated by high glucose decreased. After added adiponectin in the culture medium, the proliferation of BeWo cells treated by adiponectin+high glucose decreased than that of cells treated by high glucose (0.770±0.050 versus 0.990±0.070, P<0.05); the proportion of G2+S phases of BeWo cells treated by adiponectin+high glucose decreased than that of cells treated by high glucose [(40.7±2.1)% versus (44.9± 3.9)%, P<0.05]; the rate of PCNA positive cell in BeWo cells treated by adiponectin+high glucose decreased than that of cells treated by high glucose [(28±5)% versus (44±5)%, P<0.05]. CONCLUSION: Adiponectin could inhibit proliferation of high glucose induced BeWo cells in vitro.


Asunto(s)
Adiponectina/metabolismo , Proliferación Celular/fisiología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Western Blotting , Ciclo Celular , Citometría de Flujo , Glucosa
16.
Zhonghua Gan Zang Bing Za Zhi ; 24(1): 51-5, 2016 Jan.
Artículo en Zh | MEDLINE | ID: mdl-26983390

RESUMEN

OBJECTIVE: To retrospectively investigate the efficacy of human umbilical cord-derived mesenchymal stem cells (UC-MSC) as clinical treatment for HBV-related decompensated liver cirrhosis (HBV-DLC)•D. METHODS: Sixty patients with HBV-DLC were given standard medical treatment combined with a 3-month regimen of UC-MSC at a dose of 0.5-1.0×10(6) cells/kg/month. Another group of patients with HBV-DLC (n=120; control group) that was matched (2:1) to the case group by age, sex, diagnosis, and follow-up period was given the standard medical treatment only. We reviewed all patients' data of biochemical tests, imaging examinations, Child-Pugh scores, and adverse reactions. Comparisons of continuous data between the two groups were made by independent-sample t-test, and comparisons of categorical data were made by chi-square test. RESULTS: Compared with the control group, the group that received the combination UC-MSC treatment showed a significant rise in cholinesterase, globulin and alkaline phosphatase, and reduced Child-Pugh scores during the follow-up period. However, there was no significant difference between the groups of patients for levels of alanine transaminase, total bilirubin, albumin, total cholesterol, or prothrombin activity. CONCLUSIONS: Addition of the UC-MSC treatment to the standard therapy could help to improve liver function in patients with HBV-DLC.


Asunto(s)
Hepatitis B/terapia , Cirrosis Hepática/terapia , Trasplante de Células Madre Mesenquimatosas , Cordón Umbilical/citología , Humanos , Cirrosis Hepática/virología , Células Madre Mesenquimatosas/citología
17.
Appl Microbiol Biotechnol ; 99(2): 729-39, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25038929

RESUMEN

The Bluetongue virus (BTV) VP7 protein represents an important group-specific antigen that can serve as a basis for diagnostic tests. Here, we report the generation of a novel BTV group-specific monoclonal antibody (Mab; herein named 4H7) that recognizes a conformational epitope in the VP7 protein. We used a phage-displayed peptide screen and site-directed mutagenesis to define the VP7 amino acid residues that most strongly contribute to the conformational epitope recognized by Mab 4H7. Amino acid residues at positions 175, 185, 186, and 278 of the BTV VP7 protein strongly contributed to Mab 4H7 binding. These key amino acid residues are conserved among all BTV serotypes, whereas related Orbiviruses possess at least one amino acid substitution at these positions. We developed a competitive enzyme-linked immunosorbent assay (c-ELISA) using Mab 4H7 and recombinant BTV VP7 protein to detect serum antibodies against this BTV group-specific VP7 epitope. The c-ELISA was used to screen 833 clinical samples collected from animals in three provinces of China. BTV seroprevalence in the three provinces ranged from 25.42 to 47.45 %. This work provides the foundation for a new diagnostic c-ELISA that can be further applied to BTV surveillance activities and informs our understanding of the structure of the BTV VP7 protein.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Virus de la Lengua Azul/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Animales , Anticuerpos Monoclonales/sangre , Anticuerpos Antivirales/sangre , China , Clonación Molecular , Epítopos/sangre , Epítopos/inmunología , Cabras/virología , Mutagénesis Sitio-Dirigida , Conformación Proteica , Proteínas Recombinantes/sangre , Proteínas Recombinantes/inmunología , Reproducibilidad de los Resultados , Estudios Seroepidemiológicos , Ovinos/virología , Proteínas del Núcleo Viral/sangre , Proteínas del Núcleo Viral/inmunología
18.
Genet Mol Res ; 14(2): 4276-81, 2015 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-25966199

RESUMEN

We sought to investigate the relationship between abnormal expression of nitric oxide synthase (NOS) and pathogenesis of cerebral aneurysm. Brain tissues were collected from 36 patients with cerebral aneurysm confirmed by computer tomography with angiography or neurosurgical therapy. The control group consisted of 25 patients of similar age who had no vascular diseases, as confirmed by magnetic resonance imaging. Samples of cortical arterioles were collected. The structure of the aneurysms was detected by hematoxylin and eosin staining, and the expression of inducible NOS was detected by immunohistochemistry. NOS expression was significantly higher in the patient group than in the control group (patients: 30/36 strongly positive; control: 0/25 strongly positive; P < 0.05). In conclusion, the pathogenesis underlying cerebral aneurysm may be due to abnormal expression of NOS, degradation of the extracellular matrix, aggravation of a pro-inflammatory reaction, or a deficiency in arterial elasticity layer synthesis. These changes may result in a deficiency in vascular remodeling.


Asunto(s)
Angiografía Cerebral/métodos , Aneurisma Intracraneal/patología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico/metabolismo , Adolescente , Adulto , Femenino , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Tomografía Computarizada por Rayos X , Adulto Joven
19.
Br J Cancer ; 110(7): 1748-58, 2014 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-24569473

RESUMEN

BACKGROUND: Pelvic lymph node metastasis (PLNM) is the key to determining the treatment and prognosis of early-stage cervical cancer (CC, I-IIst). The aim of this study was to identify biomarkers for PLNM of CC, I-IIst. METHODS: Two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were used to identify differentially expressed proteins in primary CC, I-IIst tissue with (n=8) and without (n=10) PLNM. The expression levels of three differential proteins (FABP5, HspB1, and MnSOD) were validated using western blotting and immunohistochemistry. An independent cohort of 105 CC, I-IIst patients was analysed to assess the correlation of FABP5, HspB1, and MnSOD with clinicopathologic factors and clinical outcomes. RESULTS: Forty-one differential proteins were identified. Upregulation of FABP5, HspB1, and MnSOD in CC, I-IIst with PLNM was confirmed and was significantly correlated with PLNM. FABP5, HspB1, and MnSOD were significant predictors of PLNM in univariate analysis. FABP5, HspB1, and lymphovascular space invasion (LVSI) were independent predictors of PLNM in multivariate analysis. Survival curves indicated that CC, I-IIst patients with FABP5, HspB1, and MnSOD upregulation had poor prognosis. CONCLUSIONS: FABP5, HspB1, and MnSOD may be potential biomarkers for PLNM of CC, I-IIst and may have important roles in the pathogenesis of PLNM.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Ganglios Linfáticos/patología , Proteómica/métodos , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Ganglios Linfáticos/metabolismo , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Pelvis , Análisis de Matrices Tisulares
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