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1.
Proc Natl Acad Sci U S A ; 118(35)2021 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-34446548

RESUMEN

Nonlinear differential equations model diverse phenomena but are notoriously difficult to solve. While there has been extensive previous work on efficient quantum algorithms for linear differential equations, the linearity of quantum mechanics has limited analogous progress for the nonlinear case. Despite this obstacle, we develop a quantum algorithm for dissipative quadratic n-dimensional ordinary differential equations. Assuming [Formula: see text], where R is a parameter characterizing the ratio of the nonlinearity and forcing to the linear dissipation, this algorithm has complexity [Formula: see text], where T is the evolution time, ϵ is the allowed error, and q measures decay of the solution. This is an exponential improvement over the best previous quantum algorithms, whose complexity is exponential in T. While exponential decay precludes efficiency, driven equations can avoid this issue despite the presence of dissipation. Our algorithm uses the method of Carleman linearization, for which we give a convergence theorem. This method maps a system of nonlinear differential equations to an infinite-dimensional system of linear differential equations, which we discretize, truncate, and solve using the forward Euler method and the quantum linear system algorithm. We also provide a lower bound on the worst-case complexity of quantum algorithms for general quadratic differential equations, showing that the problem is intractable for [Formula: see text] Finally, we discuss potential applications, showing that the [Formula: see text] condition can be satisfied in realistic epidemiological models and giving numerical evidence that the method may describe a model of fluid dynamics even for larger values of R.

2.
Phys Rev Lett ; 131(15): 150603, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37897749

RESUMEN

We propose a simple method for simulating a general class of nonunitary dynamics as a linear combination of Hamiltonian simulation (LCHS) problems. LCHS does not rely on converting the problem into a dilated linear system problem or on the spectral mapping theorem. The latter is the mathematical foundation of many quantum algorithms for solving a wide variety of tasks involving nonunitary processes, such as the quantum singular value transformation. The LCHS method can achieve optimal cost in terms of state preparation. We also demonstrate an application for open quantum dynamics simulation using the complex absorbing potential method with near-optimal dependence on all parameters.

3.
Clin Infect Dis ; 72(6): 1016-1023, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-32100025

RESUMEN

BACKGROUND: Data on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)-positive (HBsAg+) donors to HBsAg-negative (HBsAg-) recipients [D(HBsAg+)/R(HBsAg-)] are limited. We aimed to report the outcomes of D(HBsAg+)/R(HBsAg-) KTx in recipients with or without hepatitis B surface antibody (HBsAb). METHODS: Eighty-three D(HBsAg+)/R(HBsAg-) living KTx cases were retrospectively identified. The 384 cases of KTx from hepatitis B core antibody-positive (HBcAb+) living donors to HBcAb-negative (HBcAb-) recipients [D(HBcAb+)/R(HBcAb-)] were used as the control group. The primary endpoint was posttransplant HBsAg status change from negative to postive (-- →+). RESULTS: Before KTx, 24 donors (28.9%) in the D(HBsAg+)/R(HBsAg-) group were hepatitis B virus (HBV) DNA positive, and 20 recipients were HBsAb-. All 83 D(HBsAg+)/R(HBsAg-) recipients received HBV prophylaxis, while no D(HBcAb+)/R(HBcAb-) recipients received prophylaxis. After a median follow-up of 36 months (range, 6-106) and 36 months (range, 4-107) for the D(HBsAg+)/R(HBsAg-) and D(HBcAb+)/R(HBcAb-) groups, respectively, 2 of 83 (2.41%) D(HBsAg+)/R(HBsAg-) recipients and 1 of 384 (0.26%) D(HBcAb+)/R(HBcAb-) became HBsAg+, accompanied by HBV DNA-positive (P = .083). The 3 recipients with HBsAg-→+ were exclusively HBsAb-/HBcAb- before KTx. Recipient deaths were more frequent in the D(HBsAg+)/R(HBsAg-) group (6.02% vs 1.04%, P = .011), while liver and graft function, rejection, infection, and graft loss were not significantly different. In univariate analyses, pretransplant HBsAb-/HBcAb- combination in the D(HBsAg+)/R(HBsAg-) recipients carried a significantly higher risk of HBsAg-→+, HBV DNA-→+, and death. CONCLUSIONS: Living D(HBsAg+)/R(HBsAg-) KTx in HBsAb+ recipients provides excellent graft and patient survivals without HBV transmission. HBV transmission risks should be more balanced with respect to benefits of D(HBsAg+)/R(HBsAg-) KTx in HBsAb-/HBcAb- candidates.


Asunto(s)
Hepatitis B , Trasplante de Riñón , China/epidemiología , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Humanos , Donadores Vivos , Estudios Retrospectivos , Donantes de Tejidos
4.
BMC Infect Dis ; 21(1): 41, 2021 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-33422017

RESUMEN

BACKGROUND: In order to reduce the burden on organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg) + donors to HBsAg- recipients [D (HBsAg+)/R(HBsAg-)] without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity. METHODS: We retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb) + living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary endpoint. RESULTS: Twenty-four donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, while none was applied in the D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P < 0.001). Interestingly, no significant difference was found between groups on HBV seroconversion, liver and graft function, rejection, infection, graft loss, or death. However, 2/20 recipients without HBV immunity in the D(HBsAg+)/R(HBsAg-) group developed HBV DNA+ or HBsAg+, while none observed in the D(HBcAb+)/R(HBcAb-) group. HBV DNA+ donor and male recipient were significant risk factors for treatment failure. CONCLUSION: D(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donors with HBV DNA+ and male candidates.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/genética , Hepatitis B/virología , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/virología , Adulto , Anciano , ADN Viral/genética , Femenino , Hepatitis B/sangre , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/genética , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Humanos , Riñón/virología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos/estadística & datos numéricos , Receptores de Trasplantes/estadística & datos numéricos , Insuficiencia del Tratamiento
5.
Nat Commun ; 15(1): 434, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38199993

RESUMEN

Large machine learning models are revolutionary technologies of artificial intelligence whose bottlenecks include huge computational expenses, power, and time used both in the pre-training and fine-tuning process. In this work, we show that fault-tolerant quantum computing could possibly provide provably efficient resolutions for generic (stochastic) gradient descent algorithms, scaling as [Formula: see text], where n is the size of the models and T is the number of iterations in the training, as long as the models are both sufficiently dissipative and sparse, with small learning rates. Based on earlier efficient quantum algorithms for dissipative differential equations, we find and prove that similar algorithms work for (stochastic) gradient descent, the primary algorithm for machine learning. In practice, we benchmark instances of large machine learning models from 7 million to 103 million parameters. We find that, in the context of sparse training, a quantum enhancement is possible at the early stage of learning after model pruning, motivating a sparse parameter download and re-upload scheme. Our work shows solidly that fault-tolerant quantum algorithms could potentially contribute to most state-of-the-art, large-scale machine-learning problems.

6.
Arch Pathol Lab Med ; 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38385871

RESUMEN

CONTEXT.­: Regulatory T-cell (Treg) detection in peripheral blood, based on flow cytometry, is invaluable for diagnosis and treatment of immune-mediated diseases. However, there is a lack of reliable methods to verify the performance, which is pivotal towards standardization of the Tregs assay. OBJECTIVE.­: To conduct standardization studies and verify the performance of 3 commercially available reagent sets for the Tregs assay based on flow cytometry and agreement analysis for Treg detection across the different reagent sets. DESIGN.­: The analytical performance of Tregs assay using reagent sets supplied by 3 manufacturers was evaluated after establishing the gating strategy and determining the optimal antibody concentration. Postcollection sample stability was evaluated, as well as the repeatability, reproducibility, reportable range, linearity, and assay carryover. Agreement between the different assays was assessed via Bland-Altman plots and linear regression analysis. The relationship between the frequency of CD4+CD25+CD127low/- Tregs and CD4+CD25+Foxp3+ Tregs was evaluated. RESULTS.­: The postcollection sample stability was set at 72 hours after collection at room temperature. The accuracy, repeatability, reproducibility, and accuracy all met the requirements for clinical analysis. Excellent linearity, with R2 ≥0.9 and no assay carryover, was observed. For reportable range, a minimum of 1000 events in the CD3+CD4+ gate was required for Tregs assay. Moreover, the results for Tregs labeled by antibodies from the 3 manufacturers were in good agreement. The percentage of CD4+CD25+CD127low/- Tregs was closely correlated with CD4+CD25+Foxp3+ Tregs. CONCLUSIONS.­: This is the first study to evaluate systematically the measurement performance of Tregs in peripheral blood by flow cytometry, which provides a practical solution to verifying the performance of flow cytometry-based immune monitoring projects in clinical practice.

7.
Int J Ophthalmol ; 16(12): 1942-1951, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38111935

RESUMEN

AIM: To investigate the effect of electroacupuncture (EA) on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lens-induced myopia (LIM). METHODS: Guinea pigs were randomly divided into normal control (NC) group, LIM group, LIM+SHAM acupoint (LIM+SHAM) group, and LIM+EA group. Animals in the NC group received no intervention, while those in other three groups were covered with -6.0 diopter (D) lenses on right eyes. Meanwhile, animals in the LIM+EA group received EA at Hegu (LI4) combined with Taiyang (EX-HN5) acupoints, while those in the LIM+SHAM group were treated at sham points. After treatments for 1, 2, and 4wk, morphological changes in ciliary muscles were observed with hematoxylin and eosin (H&E) staining and nick end labeling (TUNEL), and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. Additionally, the adenosine triphosphate (ATP) contents were also determined in ciliary muscles. RESULTS: Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group. The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups, whereas those in the LIM+EA group improved significantly. TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups, whereas reduced in the LIM+EA group. ATP contents showed a significant decrease in the LIM and LIM+SHAM groups, whereas increased after EA treatment. Compared with the NC group, the dynamin-related protein 1 (DRP1), Caspase3, and apoptotic protease activator 1 (APAF1) levels were significantly increased in the LIM group and decreased in the LIM+EA group. CONCLUSION: The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.

8.
Appl Phys A Mater Sci Process ; 128(12): 1065, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36406017

RESUMEN

Recently, the problem of water pollution, caused by antibiotics, is becoming more and more serious. Photocatalysis is one of the promising technologies for removing antibiotics from water. Herein, the In2.77S4/Ti3C2 composites were prepared by an in-situ hydrothermal growth method for photocatalytic degradation of tetracycline (TC). The as-developed composites were characterized by various methods. The UV-Vis DRS spectra reveals that the introduction of Ti3C2 makes the bandgap of the as-prepared composites smaller and the visible light absorption ability improved. The photocatalytic degradation efficiency of the as-prepared composite is enhanced under visible light illumination. It is shown as first increasing and then decreasing with increasing the content of Ti3C2 in the composite and reaches to the maximum of 89.3% in 90 min, which is higher than 75.1% of In2.77S4 and 6.7% of Ti3C2. The reason of improvement is the interface between In2.77S4 and Ti3C2 is tightly combined to form a heterojunction. Moreover, the photocurrent intensity of the as-obtained composite is improved, while its Nyquist arc radius is decreased. In addition, holes are the main active species and ·OH and ·O2 - play an auxiliary role during the degradation of TC.

9.
Am J Physiol Heart Circ Physiol ; 299(3): H731-42, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20622109

RESUMEN

Atherosclerosis is a chronic inflammation disease characterized by acidic micromilieu and the accumulation of numerous bioactive lipid mediators, such as lysophosphatidic acid (LPA) and prostaglandins, in the atherosclerotic lesion. Chronic acidification induced various effects on vascular smooth muscle cells, but the molecular mechanisms underlying these effects remain unknown. In this study, we examine the role of proton-sensing ovarian cancer G protein-coupled receptor 1 (OGR1) in extracellular acidification-induced regulation of cyclooxygenase (COX)-2 induction, PGI(2) production, MAPK phosphatase (MKP)-1 expression, and plasminogen activator inhibitor (PAI)-1 expression and proliferation in human aortic smooth muscle cells (AoSMCs). Experiments with knockdown with small interfering RNA specific to OGR1 and specific inhibitors for G proteins showed that acidification-induced COX-2 expression, PGI(2) production, and MKP-1 expression, but not PAI-1 expression and inhibition of proliferation, were dependent on OGR1 and mainly mediated by G(q/11) protein. LPA remarkably enhanced, through the LPA(1) receptor/G(i) protein, the OGR1-mediated vascular actions to acidic pH. In conclusion, acidic pH-induced vascular actions of AoSMCs can be dissected to OGR1-dependent and -independent pathways: COX-2 expression, PGI(2) production, and MKP-1 expression are mediated by OGR1, but PAI-1 expression and inhibition of proliferation are not. LPA, which is usually thought to be a proatherogenic lipid mediator, may exert antiatherogenic actions under acidic micromilieu through cross-talk between LPA(1)/G(i) protein and OGR1/G(q/11) protein.


Asunto(s)
Aorta/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Análisis de Varianza , Western Blotting , Células Cultivadas , AMP Cíclico/metabolismo , Ciclooxigenasa 2/metabolismo , Fosfatasa 1 de Especificidad Dual/metabolismo , Epoprostenol/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Músculo Liso Vascular/citología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Receptores Acoplados a Proteínas G/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección
10.
Pharmacol Res ; 61(6): 499-505, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20211729

RESUMEN

GPR4, previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways, including the G(s)-protein/cAMP, G(12/13)-protein/Rho, and G(q)-protein/phospholipase C pathways. In the present study, we examined whether extracellularly located histidine residues of GPR4 sense extracellular protons and, if so, whether a certain histidine residue is critical for coupling to the single or multiple signaling pathway(s). We found that the mutation of histidine residue at 79, 165, or 269 from the N-terminal of GPR4 to phenylalanine shifted the half-maximal effective concentration (EC(50)) of proton-induced signaling activities to the right, including cAMP accumulation, SRE promoter activity reflecting Rho activity, and NFAT promoter activity reflecting phospholipase C signaling activity, without an appreciable change in the maximal activities. These results suggest that the protonation of each one of histidine residues at 79, 165, and 269 in GPR4 may be critical for conformational change of the receptor for coupling to multiple intracellular signaling pathways through G-proteins.


Asunto(s)
Histidina/genética , Mutación Puntual , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal , Línea Celular , Humanos , Protones
11.
Int J Biol Macromol ; 157: 170-176, 2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32348857

RESUMEN

The 3-aminopropyltriethoxysilane modified nano-carbon sphere (MNCS) was added into pectin-Ca2+ film to improve the controlled release properties of the pectin-based oral colon-specific drug delivery system (OCDDS). The FT-IR measurements indicated the successful modification of nano-carbon sphere via silylation reaction and the electrostatic interaction between the pectin molecules and MNCS in the composite film. The FE-SEM showed the pore structure when the MNCS was mingled with the pectin. The 5-fluorouracil (5-FU) was employed as the drug model and the controlled release properties of the corresponding OCDDSs were determined. The values of the encapsulation efficiency ranged from 30.1% to 52.6%. All composite film based OCDDSs presented higher encapsulation efficiency than single pectin-Ca2+ based OCDDS. The drug release studies emerged that almost all the OCDDSs from composite films presented better release properties than single pectin-Ca2+ based OCDDS. The sample C revealed best release performance with the cumulative release rate of 32.17%, 22.77% and 63.89% in the simulated gastric fluid, small intestinal fluid and colon fluid, respectively. In addition, the kinetics studies were performed to analyze the release data. The cytotoxicity assay indicated good biocompatibility of the composite carriers.


Asunto(s)
Carbono/química , Colon/metabolismo , Portadores de Fármacos/química , Nanocompuestos/química , Nanosferas/química , Pectinas/química , Administración Oral , Fluorouracilo/administración & dosificación , Fluorouracilo/química , Geles , Especificidad de Órganos , Propilaminas/química , Silanos/química
12.
Ann Transplant ; 25: e920224, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-32029699

RESUMEN

BACKGROUND ABO-incompatible (ABOi) living-donor kidney transplantation (KTx) is well established in developed countries, but not yet in China. MATERIAL AND METHODS We developed individualized preconditioning protocols for ABOi KTx based on initial ABO antibody titers. After propensity score matching of ABOi with ABO-compatible (ABOc) KTx, post-transplant outcomes were compared. RESULTS Between September 2014 and June 2018, 48 ABOi living-donor KTx candidates received individualized preconditioning, and all underwent subsequent KTx (median initial ABO titers: 16 for IgM and 16 for IgG). Thirty-one recipients (64.6%) were preconditioned with rituximab (median dose: 200 mg, range: 100-500 mg). Among 37 patients (77.1%) who received pre-transplant antibody removal, the median number of sessions of antibody removal required to achieve ABOi KTx was 2 (range: 1-5), which was conducted between days -10 and -1. Eleven ABOi recipients (22.9%) were preconditioned with oral immunosuppressants alone. Hyperacute rejection led to the loss of 2 grafts in the ABOi group. After a median follow-up of 27.6 months (ABOi group) and 29.8 months (ABOc group), there were no significant differences in graft/recipient survival, rejection, and infection. There were marginally higher rates of severe thrombocytopenia (<50×109/L) (P=0.073) and delayed wound healing (P=0.096) in ABOi recipients. CONCLUSIONS Our individualized preconditioning protocol evolved as our experience grew, and the short-term clinical outcomes of ABOi KTx did not differ from those of matched ABOc patients. ABOi KTx may be a major step forward in expanding the kidney living-donor pool in China.


Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Incompatibilidad de Grupos Sanguíneos/inmunología , Desensibilización Inmunológica/métodos , Trasplante de Riñón/métodos , Donadores Vivos , Adulto , Anciano , China , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Medicina de Precisión , Estudios Retrospectivos , Rituximab/uso terapéutico , Receptores de Trasplantes , Adulto Joven
13.
Kaohsiung J Med Sci ; 35(6): 350-357, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30942560

RESUMEN

The present study is aimed to assess the safety and efficacy of steroid withdrawal or avoidance (SWA) in high-risk kidney transplant (HRKT). We performed a systematic review of the literature and pooled analysis of the available data concerning SWA following HRKT. HRKT is associated with patients undergoing repeat kidney transplantation, in African American recipients, or in patients with panel-reactive antibody levels >20%. Seven cohort studies and one randomized controlled trial, involving a total of 22 075 patients, were included. Pooled analysis to estimate the risk ratio (RR) and 95% confidence interval (CI) demonstrated comparable graft loss (RR = 0.91, 95% CI 0.76-1.09) between the SWA and corticosteroid maintenance groups, but with reduced mortality in the SWA group (RR = 0.90, 95% CI 0.84-0.98). A subanalysis suggested that SWA was not associated with increased graft loss in patients undergoing steroid withdrawal within 1 week of transplantation, in African American recipients, or in patients with follow-up >5 years. Additionally, SWA was associated with reduced death in those undergoing withdrawal within 1 week (RR = 0.90, 95% CI 0.84-0.98), in African Americans (RR = 0.90, 95% CI 0.83-0.98), and in those with follow-up extended to >5 years (RR = 0.91, 95% CI 0.84-0.98). SWA was not associated with an increased risk of acute rejection (RR = 0.95, 95% CI 0.75-1.21) or cytomegalovirus infection (RR = 1.86, 95% CI 1-3.47); however, it was associated with a reduced risk of posttransplant diabetes mellitus (RR = 0.60, 95% CI 0.37-0.97). SWA following HRKT is safe in terms of graft survival and rejection, and patients undergoing an SWA regimen had a lower risk of death and posttransplant diabetes mellitus. Future prospective studies are required to confirm these findings.


Asunto(s)
Corticoesteroides/efectos adversos , Diabetes Mellitus/prevención & control , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Inmunosupresores/efectos adversos , Trasplante de Riñón , Insuficiencia Renal Crónica/cirugía , Adolescente , Corticoesteroides/administración & dosificación , Adulto , Estudios de Cohortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etiología , Esquema de Medicación , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Rechazo de Injerto/fisiopatología , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Seguridad del Paciente , Insuficiencia Renal Crónica/inmunología , Insuficiencia Renal Crónica/fisiopatología
14.
Cell Signal ; 19(8): 1745-53, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17462861

RESUMEN

GPR4 was initially identified as a receptor for sphingosylphosphorylcholine and lysophosphatidylcholine; however, lipid actions have not always been confirmed. Instead, ligand-independent actions have sometimes been observed in GPR4- and other OGR1 family receptor-expressing cells. Here, we examined the possible involvement of extracellular protons, which have recently been proposed as another ligand for GPR4. At pH 7.4, the epidermal growth factor-induced extracellular signal-regulated kinase activity was lower in GPR4-transfected RH7777 cells, in association with increased cAMP accumulation, than in vector-transfected cells. The serum response element (SRE)-driven transcriptional activity was also clearly higher in GPR4-expressing HEK293 cells than in vector-transfected cells at pH 7.4. These apparent ligand-independent actions were very small at alkalinic 7.8. The SRE activity was further increased by extracellular acidification in a manner dependent on the G13 protein/Rho signaling pathway in HEK293 cells expressing GPR4 or other OGR1 receptor family members. GPR4-expressing cells also showed a calcineurin-dependent nuclear factor of activated T cell (NFAT) promoter activation at pH 7.4, and this activity was further increased by pH below 7.2 in association with inositol phosphate production. In contrast to the cAMP and SRE responses, however, alkalinization to pH 7.8 hardly affected the high basal activity. Finally, the expression of GPR4 hardly modulated the sphingosylphosphorylcholine- or lysophosphatidylcholine-induced action. These results suggest that an extracellular proton play a role as a ligand in some of previously postulated ligand-independent actions through GPR4 receptors. Moreover, GPR4 may be a multi-functional receptor coupling to Gs, G13, and Gq/11 proteins in response to extracellular acidification.


Asunto(s)
Protones , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal , Línea Celular , Línea Celular Tumoral , AMP Cíclico/biosíntesis , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Ligandos , Lisofosfatidilcolinas/metabolismo , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Fosforilcolina/análogos & derivados , Fosforilcolina/metabolismo , Elemento de Respuesta al Suero/genética , Esfingosina/análogos & derivados , Esfingosina/metabolismo
15.
Kaohsiung J Med Sci ; 34(1): 1-13, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29310811

RESUMEN

Renin-angiotensin system inhibitors, specifically angiotensin II converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), have confirmed renoprotective benefits in patients with proteinuria and hypertension. However, it remains controversial whether these agents are beneficial to kidney recipients. We conducted this meta-analysis to evaluate the effects of ACEI/ARB treatment on patient and allograft survival after kidney transplant. The PubMed, Embase and Cochrane Library databases were searched for eligible articles from before May 2016, and we included 24 articles (9 randomised controlled trials [RCTs] and 15 cohort studies with 54,096 patients), in which patient or graft survival was compared between an ACEI/ARB treatment arm and a control arm. Pooled results showed that ACEI/ARB was associated with decreased risks of patient death (relative risk [RR] = 0.64; 95% confidence interval [CI]:0.49-0.84) and graft loss (RR = 0.59; 95%CI:0.47-0.74). Subgroup analysis of the cohorts revealed significantly reduced patient death (RR = 0.61; 95%CI:0.50-0.74) and graft loss (RR = 0.58; 95%CI:0.46-0.73), but this was not seen in RCTs (patient survival: RR = 0.84, 95%CI:0.39-1.81; graft survival: RR = 0.70, 95%CI:0.17-2.79). Significantly less graft loss was noted among patients with biopsy-proved chronic allograft nephropathy (CAN) (RR = 0.26, 95%CI:0.16-0.44). Furthermore, the benefit of ACEI/ARB on patient survival (RR = 0.62; 95%CI:0.47-0.83) and graft survival (RR = 0.58, 95%CI:0.47-0.71) was limited to those with ≥3years' follow-up. ACEI/ARB decreased proteinuria (P < 0.001) and lowered haemoglobin (P = 0.002), but the haemoglobin change requires no additional treatment (from 119-131 g/L to 107-123 g/L). We therefore concluded that ACEI/ARB treatment may reduce patient death and graft loss, but additional well-designed prospective studies are needed to validate these findings.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Trasplante de Riñón/mortalidad , Sistema Renina-Angiotensina/efectos de los fármacos , Estudios de Cohortes , Humanos , Hipertensión/metabolismo , Hipertensión/mortalidad , Hipertensión/fisiopatología , Riñón/metabolismo , Riñón/patología , Riñón/cirugía , Proteinuria/metabolismo , Proteinuria/mortalidad , Proteinuria/fisiopatología , Proteinuria/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/cirugía , Análisis de Supervivencia , Trasplante Homólogo
16.
Kaohsiung J Med Sci ; 32(3): 152-9, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27106006

RESUMEN

Previous studies regarding the prevention of BK viremia following renal transplantation with fluoroquinolone have yielded conflicting results. The purpose of this systematic review was to examine the evidence regarding the efficacy of fluoroquinolone in preventing BK polyomavirus infection following renal transplantation. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for research articles published prior to January 2015 using keywords such as "fluoroquinolone," "BK viremia," and "renal transplantation." We extracted all types of study published in English. The primary outcome was BK viremia and viruria at 1 year post-transplantation. Secondary outcomes were BK virus-associated nephropathy (BKVN), graft failure, and fluoroquinolone-resistant infection. We identified eight trials, including a total of 1477 participants with a mean duration of fluoroquinolone prophylaxis of >1 month. At 1 year, fluoroquinolone prophylaxis was not associated with a decreased incidence of BK viremia [risk ratio (RR), 0.84; 95% confidence interval (95% CI), 0.58-1.20). No significant differences in BKVN (RR, 0.88; 95% CI, 0.37-2.11), risk of graft failure due to BKVN (RR, 0.68; 95% CI, 0.29-1.59), or fluoroquinolone-resistant infection (RR, 1.08; 95% CI, 0.64-1.83) were observed between the fluoroquinolone prophylaxis and control groups. The results of this study suggest that fluoroquinolone is ineffective in preventing BK polyomavirus infection following renal transplantation.


Asunto(s)
Virus BK/fisiología , Fluoroquinolonas/uso terapéutico , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/tratamiento farmacológico , Infecciones por Polyomavirus/prevención & control , Heterogeneidad Genética , Rechazo de Injerto , Humanos , Infecciones por Polyomavirus/etiología , Sesgo de Publicación , Resultado del Tratamiento
17.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 34(3): 263-6, 2005 05.
Artículo en Zh | MEDLINE | ID: mdl-15940797

RESUMEN

OBJECTIVE: To evaluate the clinical application of three-dimensional dynamic contrast-enhanced MR angiography (3D DCE MRA) in diagnosis of angiostenosis after liver transplantation. METHODS: Twenty recipients of liver transplantation underwent 3D DCE MRA examination. The blood vessel rating grades were accessed and the relative diameter of vascular anastomosis was measured; and the results were compared with those of US or DSA examination. RESULTS: Satisfactory angiography images were obtained in all cases by 3D DCE MRA, including 11 cases with normal and mild stenosis, 5 with moderate and 4 with severe stenosis in hepatic artery. Except one case in which 3D DCE MRA showed severe stenosis but DSA showed moderate stenosis, the results of MRA were all consistent with those of US or/and DSA in the stenosis degree of the portal vein, hepatic vein and the postcava. CONCLUSION: 3D DCE MRA is an effective technique to evaluate the degree of angiostenosis after liver transplantation.


Asunto(s)
Trasplante de Hígado/efectos adversos , Hígado/irrigación sanguínea , Angiografía por Resonancia Magnética , Adulto , Constricción Patológica/diagnóstico , Medios de Contraste , Femenino , Arteria Hepática/patología , Venas Hepáticas/patología , Humanos , Aumento de la Imagen , Imagenología Tridimensional , Angiografía por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Vena Porta/patología
18.
Immunol Res ; 52(3): 250-7, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22539131

RESUMEN

Selective interference with CD45RB isoform by monoclonal antibody (anti-CD45RBmAb) reliably induces donor-specific tolerance. Dendritic cells (DCs) are the most potent antigen-presenting cells that are capable of activating naïve T cells. The purposes of the present study were to investigate the roles of anti-CD45RBmAb on the phenotypes and functioning of DCs and to further illustrate the mechanism of anti-CD45RBmAb-inducing immunologic tolerance. DCs from C57BL/6 mice were cultured and treated with various doses of anti-CD45RB monoclonal antibody. Cell phenotype, cycle and phagocytic ability were detected by flow cytometry. The production of IL-10 and IL-12 in the supernatants of mature DCs was measured with ELISA. Exosomes (Dex) were recovered from the supernatant of DCs cultured for 6 days in depleted medium, and effects of DCs and Dex on the ability of T-cell proliferation were detected by mixed lymphocyte culture. Anti-CD45RBmAb could inhibit DCs maturation in a dose-dependent manner, and the effects of exosomes (Dex) on DCs enhance or inhibition proliferation of T cells were also in a dose-dependent manner. Anti-CD45RBmAb could profoundly inhibit the maturation and functioning of DCs and generate tolerogenic dendritic cells (tDCs) as well as Dex, suggesting mechanistic contributions to tolerance development from the DCs through interactions with T cells.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/farmacología , Proliferación Celular/efectos de los fármacos , Células Dendríticas/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Antígenos Comunes de Leucocito/inmunología , Linfocitos T/inmunología , Animales , Anticuerpos Monoclonales de Origen Murino/inmunología , Comunicación Celular/efectos de los fármacos , Comunicación Celular/inmunología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Tolerancia Inmunológica/inmunología , Interleucina-10/inmunología , Interleucina-12/inmunología , Antígenos Comunes de Leucocito/antagonistas & inhibidores , Ratones , Ratones Endogámicos BALB C
19.
Antiviral Res ; 87(2): 235-41, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20553764

RESUMEN

A DNA vaccine against infectious laryngotracheitis virus (ILTV) can induce specific humoral and cell-mediated immunity. However, compared to conventional vaccines, DNA vaccines usually induce poor antibody responses. To determine if co-expression of a cytokine can result in a more potent ILTV DNA vaccine, immunogenicity and protective efficacy of a monocistronic vector encoding the glycoprotein B (gB) of ILTV was compared to that of a bicistronic vector separately encoding the gB and chicken interleukin-18. Humoral and cellular responses induced by the DNA vaccines administered to the quadriceps muscle of chickens were evaluated. There were significant differences in antibody levels elicited by either monocistronic or bicistronic DNA vaccines as determined by ELISA. The percentages of CD3(+), CD3(+)CD8(+) and CD3(+)CD4(+) subgroups of peripheral blood T-lymphocytes in chickens immunized with the bicistronic DNA vaccine were higher than those in chickens immunized with monocistronic DNA vaccine. When chickens were challenged with a virulent CG strain of ILTV, the protective efficacy was enhanced significantly after immunization with the bicistronic DNA vaccine. These results demonstrated that co-expression of an adjuvant cytokine from a bicistronic DNA vaccine may be an effective approach to increasing ILTV DNA vaccine immunogenicity.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Herpesvirus Gallináceo 1/inmunología , Interleucina-18/farmacología , Vacunas de ADN/inmunología , Proteínas del Envoltorio Viral/inmunología , Adyuvantes Inmunológicos/genética , Animales , Anticuerpos Antivirales/sangre , Complejo CD3/análisis , Antígenos CD4/análisis , Antígenos CD8/análisis , Pollos , Ensayo de Inmunoadsorción Enzimática , Herpesvirus Gallináceo 1/genética , Inyecciones Intramusculares , Interleucina-18/genética , Análisis de Supervivencia , Subgrupos de Linfocitos T/química , Subgrupos de Linfocitos T/inmunología , Vacunas de ADN/genética , Proteínas del Envoltorio Viral/genética
20.
FEMS Immunol Med Microbiol ; 57(2): 129-35, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19732142

RESUMEN

To evaluate the effects of recombinant porcine interleukin-18 (rpIL-18) on the replication of viruses in host cells and proliferation of lymphocytes, porcine IL-18 (pIL-18) isolated from a domestic big-white porcine breed found in the Henan province (HN) was cloned using a reverse transcriptase-PCR. The cloned HN pIL-18 contained an ORF of 579 base pairs encoding a 192-amino-acid precursor protein. The amino acid sequence of HN pIL-18 was compared with all the other pIL-18 amino acid sequences and varied by at least one amino acid to the consensus of all the others available. HN pIL-18 mature protein gene was inserted into a prokaryotic vector pGEX-4T-1 and expressed in Escherichia coli BL21. The expression of glutathione-S-transferase-pIL18 fusion protein was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. The rpIL-18 induced in vitro proliferation of concanavalin-A-stimulated porcine splenocytes, as revealed by the MTT assay. We studied the antiviral activities of the rpIL-18 on the replication of porcine reproductive and respiratory syndrome virus (PRRSV), pseudorabies virus (PRV), and porcine parvovirus (PPV) cultured in two homologous cell lines. The results suggested that rpIL-18 can stimulate the proliferation of lymphocytes and inhibit viral pathogens infecting the porcine population.


Asunto(s)
Interleucina-18/genética , Interleucina-18/farmacología , Animales , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular , China , Clonación Molecular/métodos , Efecto Citopatogénico Viral , Escherichia coli/genética , Escherichia coli/metabolismo , Herpesvirus Suido 1/fisiología , Interleucina-18/biosíntesis , Interleucina-18/aislamiento & purificación , Activación de Linfocitos/efectos de los fármacos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Parvovirus Porcino/fisiología , Filogenia , Reacción en Cadena de la Polimerasa , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/farmacología , Análisis de Secuencia de Proteína , Porcinos , Replicación Viral/efectos de los fármacos
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