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1.
BMC Musculoskelet Disord ; 25(1): 319, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654270

RESUMEN

BACKGROUND: To evaluate the effectiveness of instrument-assisted soft tissue mobilization (IASTM) on range of motion (ROM). METHODS: We performed a literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to December 23, 2023. Randomized controlled trials that compared treatment groups receiving IASTM to controls or IASTM plus another treatment(s) to other treatment(s) among healthy individuals with or without ROM deficits, or patients with musculoskeletal disorders were included. The Cochrane risk of bias tool was used to assess the risk of bias. RESULTS: Nine trials including 450 participants were included in the quantitative analysis. The IASTM was effective in improving ROM in degree in healthy individuals with ROM deficits and patients with musculoskeletal disorders (n=4) (MD = 4.94, 95% CI: 3.29 to 6.60), and in healthy individuals without ROM deficits (n=4) (MD = 2.32, 95% CI: 1.30 to 3.34), but failed to improve ROM in centimeter in healthy individuals with ROM deficits (n=1) (MD = 0.39, 95% CI: -1.34 to 2.11, p=0.66, I2 = 88%). CONCLUSIONS: IASTM can improve ROM in degree in healthy individuals with or without ROM deficits, or in patients with musculoskeletal disorders (with very low to low certainty). TRIAL REGISTRATION: The PROSPERO registration ID is CRD42023425200.


Asunto(s)
Enfermedades Musculoesqueléticas , Rango del Movimiento Articular , Humanos , Rango del Movimiento Articular/fisiología , Enfermedades Musculoesqueléticas/fisiopatología , Enfermedades Musculoesqueléticas/terapia , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos
2.
J Virol ; 89(8): 4549-61, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25673719

RESUMEN

UNLABELLED: Highly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and continue to be a pandemic threat. While vaccines are available, other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. To produce a therapeutic agent that is highly efficacious at low doses and is broadly specific against antigenically drifted H5N1 influenza viruses, we developed two neutralizing monoclonal antibodies and combined them into a single bispecific Fc fusion protein (the Fc dual-affinity retargeting [FcDART] molecule). In mice, a single therapeutic or prophylactic dose of either monoclonal antibody at 2.5 mg/kg of body weight provided 100% protection against challenge with A/Vietnam/1203/04 (H5N1) or the antigenically drifted strain A/Whooper swan/Mongolia/244/05 (H5N1). In ferrets, a single 1-mg/kg prophylactic dose provided 100% protection against A/Vietnam/1203/04 challenge. FcDART was also effective, as a single 2.5-mg/kg therapeutic or prophylactic dose in mice provided 100% protection against A/Vietnam/1203/04 challenge. Antibodies bound to conformational epitopes in antigenic sites on the globular head of the hemagglutinin protein, on the basis of analysis of mutants with antibody escape mutations. While it was possible to generate escape mutants in vitro, they were neutralized by the antibodies in vivo, as mice infected with escape mutants were 100% protected after only a single therapeutic dose of the antibody used to generate the escape mutant in vitro. In summary, we have combined the antigen specificities of two highly efficacious anti-H5N1 influenza virus antibodies into a bispecific FcDART molecule, which represents a strategy to produce broadly neutralizing antibodies that are effective against antigenically diverse influenza viruses. IMPORTANCE: Highly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and are a pandemic threat. A vaccine is available, but other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. The variability of the virus means that such an approach must be broad spectrum. To achieve this, we developed two antibodies that neutralize H5N1 influenza viruses. In mice, these antibodies provided complete protection against a spectrum of H5N1 influenza viruses at a single low dose. We then combined the two antibodies into a single molecule, FcDART, which combined the broad-spectrum activity and protective efficacy of both antibodies. This treatment provides a novel and effective therapeutic agent or prophylactic with activity against highly pathogenic H5N1 avian influenza viruses.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/uso terapéutico , Subtipo H5N1 del Virus de la Influenza A/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Animales , Células CHO , Cricetinae , Cricetulus , Perros , Hurones , Técnica del Anticuerpo Fluorescente , Células HEK293 , Pruebas de Inhibición de Hemaglutinación , Humanos , Células de Riñón Canino Madin Darby , Ratones , Pruebas de Neutralización , Infecciones por Orthomyxoviridae/inmunología
3.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(5): 1193-8, 2015 May.
Artículo en Zh | MEDLINE | ID: mdl-26415426

RESUMEN

In the present work, computer simulation was performed on a model chemical system where two solutes (denoted as P and Q, respectively) are dissolved in the same solution. Under intermolecular interaction between P and Q, part of P undergoes subtle structural variation and converts into U while part of Q converts into V. The strength of intermolecular interaction can be characterized by the corresponding equilibrium constant K. Our preliminary studies indicate that the S/N ratio of cross peak increases considerably as n increases. Moreover, the S/N ratio of the cross peak from the asynchronous spectra can be improved significantly when the suitable concentrations of P and Q are adopted. This work is helpful for a selection of suitable concentration sequence to maximize S/N ratio of cross peaks in the 2D asynchronous spectra generated by using the DAOSD approach proposed in our previous study so that weak intermolecular interaction can be probed.

4.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(8): 2241-5, 2015 Aug.
Artículo en Zh | MEDLINE | ID: mdl-26672302

RESUMEN

We reported a new super-concentrated hydrochloric acid system prepared by using tri-n-butyl phosphate (TBP)-constructed reversed micelles at ambient temperature and pressure. According to the titration result, the molar ratio of H+ to H2O (denoted as nH+/nH2O) in the super-concentrated HCl range from 0.50 to 1.50 which are higher than that in saturated aqueous HCl bulk solution (0.28). Significant a moment of hydrochloric acid is confined in W/O reversed micelles. Therefore, the behavior and status of HCl are different from those of conventional bluk solution. FTIR spectroscopic results demonstrate that a significant amount of HCl remains in the molecular form rather than being ionized into H+ and Cl-. Thus, super-concentrated HCl provides an extraordinary chemical environment which may have significant influence on certain substances. We found that the color of the solution is reddish brown when copper ion is dissolved in super-concentrated HCl, while the color of the saturated HCl aqueous solution (37 Wt%) containing copper ion is green. That is to say, the copper ions exist in a special state under the unique chemical environment of super-concentrated HCl. UV-Vis-NIR spectra indicate that both d-d transition band and charge transfer transition band of copper ions in super-concentrated HCl solution underwent significant variations. In addition, copper ions also have obvious influence on the hydrogen bond network among HCl in the super-concentrated HCl solution. Remarkable variation is introduced in the H-Cl stretching band in FTIR spectra.

5.
Artículo en Zh | MEDLINE | ID: mdl-26653232

RESUMEN

OBJECTIVE: To investigate the effects of different concentrations of paraquat (PQ) poisoning on the expression of voltage-dependent anion channel (VDAC) and caspase family in the mitochondria of rat lung tissue, and to explore possible mechanisms of acute lung injury induced by acute PQ poisoning. METHODS: Two hundred healthy adult Wister rats with equal numbers of male and female ones were randomly and equally divided into control group and poisoned group. The control group received one-time gastric lavage with 1 ml of normal saline, and the poisoned group with PQ (50 mg/kg) diluted in 1 ml of normal saline. Twenty rats were collected at 1, 24, 72, 120, and 168 h after lavage with normal saline or PQ and dissected after anesthesia. Mitochondria were separated from rat lung tissue, and the content of VDAC and caspase-3, -8, and -9 were determined. RESULTS: The expression of VDAC and caspase-3, -8, and -9 in the poisoned rats were significantly higher than that in the control group (P < 0.001). At 1, 24, 72, 120, and 168 h after exposure, acute diffuse damages were found in alveolar capillary endothelial cells, alveolar epithelial cells, and pulmonary interstitial cells. Inflammatory cell infiltration in the pulmonary interstitium, alveolar structural disorder, and substantially increased fibroblasts were also found in rat lung tissue. CONCLUSION: PQ poisoning can up-regulate the expression of VDAC and caspase-3, -8, and -9 in mitochondria of rat lung tissue to induce acute lung injury.


Asunto(s)
Lesión Pulmonar Aguda/patología , Caspasas/metabolismo , Mitocondrias/efectos de los fármacos , Paraquat/envenenamiento , Canales Aniónicos Dependientes del Voltaje/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Animales , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Femenino , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Mitocondrias/metabolismo , Ratas , Ratas Sprague-Dawley
6.
J Virol ; 87(1): 37-51, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23097455

RESUMEN

A challenge for hepatitis C virus (HCV) vaccine development is defining conserved epitopes that induce protective antibodies against this highly diverse virus. An envelope glycoprotein (E2) segment located at amino acids (aa) 412 to 423 contains highly conserved neutralizing epitopes. While polyclonal antibodies to aa 412 to 423 from HCV-infected individuals confirmed broad neutralization, conflicting findings have been reported on polyclonal antibodies to an adjacent region, aa 434 to 446, that may or may not interfere with neutralization by antibodies to aa 412 to 423. To define the interplay between these antibodies, we isolated human monoclonal antibodies (HMAbs) to aa 412 to 423, designated HC33-related HMAbs (HC33 HMAbs), and characterized their interactions with other HMAbs to aa 434 to 446. A subset of the HC33 HMAbs neutralized genotype 1 to 6 infectious cell culture-derived HCV virions (HCVcc) with various activities. Although nonneutralizing HC33 HMAbs were isolated, they had lower binding affinities than neutralizing HC33 HMAbs. These antibodies could be converted to neutralizing antibodies by affinity maturation. Unidirectional competition for binding to E2 was observed between HC33 HMAbs and HMAbs to aa 434 to 446. When HMAbs to aa 434 to 446, which mediated neutralization, were combined with neutralizing HC33 HMAbs, biphasic patterns in neutralization were observed. A modest degree of antagonism was observed at lower concentrations, and a modest degree of synergism was observed at higher concentrations. However, the overall effect was additive neutralization. A similar pattern was observed when these antibodies were combined to block E2 binding to the HCV coreceptor, CD81. These findings demonstrate that both of these E2 regions participate in epitopes mediating virus neutralization and that the antibodies to aa 412 to 423 and aa 434 to 446 do not hinder their respective virus-neutralizing activities.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Proteínas del Envoltorio Viral/inmunología , Anticuerpos Monoclonales/aislamiento & purificación , Anticuerpos Neutralizantes/aislamiento & purificación , Anticuerpos Antivirales/aislamiento & purificación , Línea Celular , Epítopos de Linfocito B/inmunología , Hepacivirus/inmunología , Humanos
7.
PLoS Pathog ; 8(4): e1002653, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22511875

RESUMEN

The majority of broadly neutralizing antibodies to hepatitis C virus (HCV) are against conformational epitopes on the E2 glycoprotein. Many of them recognize overlapping epitopes in a cluster, designated as antigenic domain B, that contains residues G530 and D535. To gain information on other regions that will be relevant for vaccine design, we employed yeast surface display of antibodies that bound to genotype 1a H77C E2 mutant proteins containing a substitution either at Y632A (to avoid selecting non-neutralizing antibodies) or D535A. A panel of nine human monoclonal antibodies (HMAbs) was isolated and designated as HC-84-related antibodies. Each HMAb neutralized cell culture infectious HCV (HCVcc) with genotypes 1-6 envelope proteins with varying profiles, and each inhibited E2 binding to the viral receptor CD81. Five of these antibodies neutralized representative genotypes 1-6 HCVcc. Epitope mapping identified a cluster of overlapping epitopes that included nine contact residues in two E2 regions encompassing aa418-446 and aa611-616. Effect on virus entry was measured using H77C HCV retroviral pseudoparticles, HCVpp, bearing an alanine substitution at each of the contact residues. Seven of ten mutant HCVpp showed over 90% reduction compared to wild-type HCVpp and two others showed approximately 80% reduction. Interestingly, four of these antibodies bound to a linear E2 synthetic peptide encompassing aa434-446. This region on E2 has been proposed to elicit non-neutralizing antibodies in humans that interfere with neutralizing antibodies directed at an adjacent E2 region from aa410-425. The isolation of four HC-84 HMAbs binding to the peptide, aa434-446, proves that some antibodies to this region are to highly conserved epitopes mediating broad virus neutralization. Indeed, when HCVcc were passaged in the presence of each of these antibodies, virus escape was not observed. Thus, the cluster of HC-84 epitopes, designated as antigenic domain D, is relevant for vaccine design for this highly diverse virus.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Epítopos/inmunología , Hepacivirus/inmunología , Proteínas del Envoltorio Viral/inmunología , Internalización del Virus , Anticuerpos Monoclonales/farmacología , Anticuerpos Neutralizantes/farmacología , Anticuerpos Antivirales/farmacología , Antígenos Virales/genética , Mapeo Epitopo/métodos , Epítopos/genética , Femenino , Genotipo , Células HEK293 , Hepacivirus/genética , Hepatitis C/genética , Hepatitis C/inmunología , Hepatitis C/prevención & control , Humanos , Masculino , Mutación , Proteínas del Envoltorio Viral/genética , Vacunas contra Hepatitis Viral
8.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(9): 2346-50, 2014 Sep.
Artículo en Zh | MEDLINE | ID: mdl-25532323

RESUMEN

The authors tried to establish an approach to use acids to convert biomass into a fuel with higher carbon content and lower oxygen content in a zero-energy-consumption fashion. Considering that biomass is composed of monosaccharide, we used aqueous solutions of variation acids including hydrochloric acid, sulfuric acid and perchloric acid to treat 2-deoxy-ribose and fructose at ambient temperature and pressure. Black substances were produced after a period of time when 2-deoxy-ribose and fructose were mixed with aqueous solutions containing 8 mol · L(-1) acids. The black substance was collected and characterized by using elemental analysis, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). Elemental analysis results indicate that the contents of carbon increases significantly in the black substances in comparison with 2-deoxy-ribose and fructose. Moreover, XPS results indicate that the content of oxygen in the black substance undergoes a significant decrease compared with pure 2-deoxy-ribose and fructose. In the XPS spectra, the is peaks of 2-deoxy-ribose, strong sub peak at 286. 05 eV, which is assigned to carbon linked to oxygen directly, dominate in the C is peak envelop. After treatment by HClO4, the peak decreased dramatically. This result also supports the conclusion that the content of oxygen in mono-saccharide is significantly reduced after treatment by acids. In the FTIR spectra of the black substances, strong peaks can be observed around 1 600 cm(-1), indicating that C==C bond is formed in the product. The above results suggest that treatments with acids may be developed as a new zero-energy-consumption approach to convert biomass in a new fuel with improved energy output efficiency.


Asunto(s)
Ácidos/química , Biocombustibles , Carbohidratos/química , Carbono/química , Espectroscopía Infrarroja por Transformada de Fourier , Biomasa , Oxígeno , Espectroscopía de Fotoelectrones
9.
Am J Emerg Med ; 31(9): 1322-7, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23928327

RESUMEN

BACKGROUND: Whether bilevel positive airway pressure (BiPAP) is advantageous compared with continuous positive airway pressure (CPAP) in acute cardiogenic pulmonary edema (ACPO) remains uncertain. The aim of the meta-analysis was to assess potential beneficial and adverse effects of CPAP compared with BiPAP in patients with ACPO. METHODS: Randomized controlled trials comparing the treatment effects of BiPAP with CPAP were identified from electronic databases and reference lists from January 1966 to December 2012. Two reviewers independently assessed study quality. In trials that fulfilled inclusion criteria, we critically evaluate the evidence for the use of noninvasive ventilation on rates of hospital mortality, endotracheal intubation, myocardial infarction, and the length of hospital stay. Data were combined using Review Manager 4.3 (The Cochrane Collaboration, Oxford, UK). Both pooled effects and 95% confidence intervals (CIs) were calculated. RESULTS: Twelve randomized controlled trials with a total of 1433 patients with ACPO were included. The hospital mortality (relative risk [RR], 0.86; 95% CI, 0.65-1.14; P = .46; I(2) = 0%) and need for requiring invasive ventilation (RR, 0.89; 95% CI, 0.57-1.38; P = .64; I(2) = 0%) were not significantly different between patients treated with CPAP and those treated with BiPAP. The occurrence of new cases of myocardial infarction (RR, 0.95; 95% CI, 0.77-1.17; P = .53, I(2) = 0%) and length of hospital stay (RR, 1.01; 95% CI, -0.40 to 2.41; P = .98; I(2) = 0%) were also not significantly different between the 2 groups. CONCLUSIONS: There are no significant differences in clinical outcomes when comparing CPAP vs BiPAP. Based on the limited data available, our results suggest that there are no significant differences in clinical outcomes when comparing CPAP with BiPAP.


Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Edema Pulmonar/terapia , Mortalidad Hospitalaria , Humanos , Edema Pulmonar/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
10.
Risk Manag Healthc Policy ; 16: 1287-1295, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37484703

RESUMEN

Background: The number of patients with thrombocytopenia (TCP) is relatively high in intensive care units (ICUs). It is therefore necessary to evaluate the prognostic risk of such patients. Aim: This study investigated the risk factors affecting the survival of patients with TCP in the ICU. Using the findings of this investigation, we developed and validated a risk prediction model. Methods: We evaluated patients admitted to the ICU who presented with TCP. We used LASSO regression to identify important clinical indicators. Based on these indicators, we developed a prediction model complete with a nomogram for the development cohort set. We then evaluated the mode's accuracy using a receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA) in a validation cohort. Results: A total of 141 cases of ICU TCP were included in the sample, of which 47 involved death of the patient. Clinical results were as follows: N (HR 0.91, 95% CI 0.86-0.97, P=0.003); TBIL (HR 1.98, 95% CI 1.02-1.99, P=0.048); APACHE II (HR 1.94, 95% CI 1.39, 2.48, P=0.045); WPRN (HR 6.22, 95% CI 2.86-13.53, P<0.001); WTOST (HR 0.56, 95% CI 0.21-1.46, P<0.001); and DMV [HR1.87, 95% CI 1.12-2.33]. The prediction model yielded an area under the curve (AUC) of 0.918 (95% CI 0.863-0.974) in the development cohort and 0.926 (95% CI 0.849-0.994) in the validation cohort. Application of the nomogram in the validation cohort gave good discrimination (C-index 0.853, 95% CI 0.810-0.922) and good calibration. DCA indicated that the nomogram was clinically useful. Conclusion: The individualized nomogram developed through our analysis demonstrated effective prognostic prediction for patients with TCP in ICUs. Use of this prediction metric may reduce TCP-related morbidity and mortality in ICUs.

11.
Ir J Med Sci ; 192(5): 2285-2290, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36637678

RESUMEN

BACKGROUND: Venous catheters are widely used in clinical practice, but a drawback of their usage is the increased risk of thrombosis. AIMS: The current study explored the risk factors affecting the formation of thrombosis following venous catheterization and establishes a risk nomogram prediction model for catheter-related thrombosis. METHODS: Univariate and multivariate logistic regression analyses were carried out to identify the independent factors involved in venous catheter thrombosis. These factors were included in the construction of a nomogram. Finally, the C-index and calibration curves were used to validate the nomogram. RESULT: A total of 146 cases were included in the sample, of which 36 were cases of thrombosis. The results of the univariate logistic regression analysis showed that the following were significant factors: age, Acute Physiology and Chronic Health Evaluation scoring system (APACHE II) score, white blood cell (WBC), hematocrit (HCT), international normalized ratio (INR), fibrinogen (FIB), and D-dimer. Multivariate logistic regression analysis was performed, which confirmed that the factors of age (AUC: 0.677, 95% CI: 0.564-0.790), APACHE II score (AUC: 0.746, 95% CI: 0.656-0.837), INR (AUC: 0.743, 95% CI: 0.636-0.849), and D-dimer (AUC: 0.826, 95% CI: 0.750-0.902) were independent variables. Next, a nomogram was constructed using these independent variables for predicting venous catheter thrombosis. Favorable results with C-indexes (0.816; 95% CI: 0.780-0.882) and calibration curves closer to ideal curves indicated the accurate predictive ability of this nomogram. CONCLUSION: The individualized nomogram demonstrated effective prognostic prediction for patients with venous thrombosis.


Asunto(s)
Trombosis , Trombosis de la Vena , Humanos , Nomogramas , Estudios Retrospectivos , Trombosis de la Vena/etiología , Trombosis/etiología , Catéteres , Cateterismo/efectos adversos
12.
Sci China Life Sci ; 66(4): 892, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36598622

RESUMEN

This paper contains errors in the authors' affiliations. Wenjia Li, is a Ph.D. candidate in the University of Chinese Academy of Sciences, Jiangchun Wei and Xingzhong Liu are professors in the University of Chinese Academy of Sciences, which is missing in the original version. The affiliations have been corrected.

13.
J Biol Chem ; 286(51): 44218-44233, 2011 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-22002064

RESUMEN

A potent neutralizing antibody to a conserved hepatitis C virus (HCV) epitope might overcome its extreme variability, allowing immunotherapy. The human monoclonal antibody HC-1 recognizes a conformational epitope on the HCV E2 glycoprotein. Previous studies showed that HC-1 neutralizes most HCV genotypes but has modest potency. To improve neutralization, we affinity-matured HC-1 by constructing a library of yeast-displayed HC-1 single chain Fv (scFv) mutants, using for selection an E2 antigen from one of the poorly neutralized HCVpp. We developed an approach by parallel mutagenesis of the heavy chain variable (VH) and κ-chain variable (Vk) genes separately, then combining the optimized VH and Vk mutants. This resulted in the generation of HC-1-related scFv variants exhibiting improved affinities. The best scFv variant had a 92-fold improved affinity. After conversion to IgG1, some of the antibodies exhibited a 30-fold improvement in neutralization activity. Both surface plasmon resonance and solution kinetic exclusion analysis showed that the increase in affinity was largely due to a lowering of the dissociation rate constant, Koff. Neutralization against a panel of HCV pseudoparticles and infectious 2a HCV virus improved with the affinity-matured IgG1 antibodies. Interestingly, some of these antibodies neutralized a viral isolate that was not neutralized by wild-type HC-1. Moreover, propagating 2a HCVcc under the selective pressure of WT HC-1 or affinity-matured HC-1 antibodies yielded no viral escape mutants and, with the affinity-matured IgG1, needed 100-fold less antibody to achieve complete virus elimination. Taken together, these findings suggest that affinity-matured HC-1 antibodies are excellent candidates for therapeutic development.


Asunto(s)
Anticuerpos Monoclonales/química , Hepacivirus/metabolismo , Pruebas de Neutralización/métodos , Anticuerpos/química , Afinidad de Anticuerpos , Separación Celular , Epítopos/química , Células HEK293 , Hepacivirus/inmunología , Humanos , Fragmentos de Inmunoglobulinas/química , Inmunoglobulina G/química , Inmunoterapia/métodos , Cinética , Microscopía Fluorescente/métodos , Mutación
14.
J Virol ; 85(20): 10451-63, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21813602

RESUMEN

Understanding the interaction between broadly neutralizing antibodies and their epitopes provides a basis for the rational design of a preventive hepatitis C virus (HCV) vaccine. CBH-2, HC-11, and HC-1 are representatives of antibodies to overlapping epitopes on E2 that mediate neutralization by blocking virus binding to CD81. To obtain insights into escape mechanisms, infectious cell culture virus, 2a HCVcc, was propagated under increasing concentrations of a neutralizing antibody to isolate escape mutants. Three escape patterns were observed with these antibodies. First, CBH-2 escape mutants that contained mutations at D431G or A439E, which did not compromise viral fitness, were isolated. Second, under the selective pressure of HC-11, escape mutations progressed from a single L438F substitution at a low antibody concentration to double substitutions, L438F and N434D or L438F and T435A, at higher antibody concentrations. Escape from HC-11 was associated with a loss of viral fitness. An HCV pseudoparticle (HCVpp) containing the L438F mutation bound to CD81 half as efficiently as did wild-type (wt) HCVpp. Third, for HC-1, the antibody at a critical concentration completely suppressed viral replication and generated no escape mutants. Epitope mapping revealed contact residues for CBH-2 and HC-11 in two regions of the E2 glycoprotein, amino acids (aa) 425 to 443 and aa 529 to 535. Interestingly, contact residues for HC-1 were identified only in the region encompassing aa 529 to 535 and not in aa 425 to 443. Taken together, these findings point to a region of variability, aa 425 to 443, that is responsible primarily for viral escape from neutralization, with or without compromising viral fitness. Moreover, the region aa 529 to 535 is a core CD81 binding region that does not tolerate neutralization escape mutations.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Epítopos/inmunología , Hepacivirus/inmunología , Mutación Missense , Proteínas del Núcleo Viral/metabolismo , Proteínas del Envoltorio Viral/inmunología , Sustitución de Aminoácidos , Mapeo Epitopo , Epítopos/genética , Hepacivirus/genética , Hepacivirus/crecimiento & desarrollo , Humanos , Unión Proteica , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo
15.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(1): 118-22, 2012 Jan.
Artículo en Zh | MEDLINE | ID: mdl-22497141

RESUMEN

In the present work, we prepared nylon 6 crystals via crystallization of nylon from phosphoric acid by using the vapors of ammonium hydroxide as a precipitation regent. Both XRD and FTIR results demonstrate that the obtained nylon 6 sample exhibit characteristic peaks of nylon 6 in gamma form. In addition, treatment of nylon 6 in boiling water for half an hour followed by FTIR and XRD characterization shows that the obtained nylon 6 sample is in gamma form rather than in meta-stable b form. DSC characterization indicates that the nylon 6 sample exhibits two melting peaks (213 and 220 degrees C) when the sample is heated at a heating rate of 10 degrees C x min(-1). The reason for this phenomenon is that the nylon 6 sample has different lamellar thickness. To investigate the thermal behavior of the nylon 6 sample, the sample underwent the following thermal treatment procedure. First, the sample was heated to a pre-set temperature (T(s)) and kept at that temperature for an hour. Subsequently, the sample was cooled down to 100 degrees C at a cooling rate of 1 degrees C x min(-1), and then cooled down to room temperature at a cooling rate of 10 degrees C x min(-1). The treated samples were characterized by FTIR and DSC method. Experimental results show that the treated nylon 6 samples exhibit different crystalline behavior. When T. ranges from 130 to 160 degrees C, no significant changes were observed. When T(s) is 170 degrees C, a small fraction nylon 6 crystals is destroyed and recrystallized into thin lamellae in a form. As a result, a pre-melting peak appears in DSC result. The pre-melting peak moves to higher temperature and its peak area increases significantly upon increasing T(s) from 170 to 198 degrees C. When T(s) amounts to 200 degrees C, the pre-melting peak and the melting peaks 213 degrees C merge into one melting peak and two melting peaks are observed at 212 and 220 degrees C in the DSC results. FTIR spectra indicate that significant amount of crystalline nylon 6 in a form appears but the majority of crystalline phase of the sample is still gamma phase. As T(s) increases from 200 to 209 degrees C, the melting peak at lower temperature moves to higher temperature with increasing its peak area. On the other hand, the melting peak at 220 degrees C decreases in intensity but does not show any peak shift. As T(s) reaches 209 degrees C, the two melting peaks merge into one peak and FTIR results demonstrate that nylon 6 in a form becomes dominate phase in the sample. In the whole heat-treatment process, the gamma phase nylon 6 sample began to transform to a phase at the heat-treatment temperature of 170 degrees C, which is far below the melting point of the original sample (221 degrees C). This is different from the results reported in the literature, which state that gamma phase nylon 6 will not transform to alpha-phase until nylon is melt.

16.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(7): 1790-4, 2012 Jul.
Artículo en Zh | MEDLINE | ID: mdl-23016326

RESUMEN

In situ TLC/FTIR technique has tremendous potential in the analysis of complex mixtures. However, the progress in this technique was quite slow. The reason is that conventional stationary phase has strong absorption in FTIR spectrum and thus brings about severe interference in the detection of samples. To solve the problem, the authors propose to use AgI fine particles as stationary phase of TLC plate. The reasons are as follows: Silver iodide fine particles have no absorbance in an IR region between 4 000 and 800 cm(-1), therefore, the interference caused by IR absorption of stationary phase can be removed. Moreover, silver iodide is stable and insolvable in water and organic solvents and thus it will not be destroyed by mobile phase or react with samples during the TLC separation. To improve TLC separation efficiency and quality of FTIR spectra during the TLC/FTIR analysis, the size of AgI particles should be below 500 nm. We used orthogonal design approach to optimize the experimental condition to AgI particles so that the average size of AgI particles is around 100 nm. No absorption of impurity or adsorbed water were observed in FTIR spectrum of the AgI particles the authors used "settlement volatilization method" to prepare TLC plate without using polymeric adhesive that may bring about significant interference in FTIR analysis. Preliminary TLC experiments proved that the TLC plate using AgI fine particles as stationary phase can separate mixtures of rhodamine B and bromophenol blue successfully. Applications of silver iodide fine particles as stationary phase have bright perspective in the development of in-situ TLC/FTIR analysis techniques.

17.
Ann Transl Med ; 10(24): 1363, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36660726

RESUMEN

Background: Sepsis-induced liver dysfunction is believed to be an independent risk factor for multiple organ dysfunction and death. Idebenone (IDE), a synthetic analog of coenzyme Q10 (CoQ10), possesses an antioxidizing property. The present study aimed to investigate the efficacy of IDE on sepsis-induced liver injury and discuss its reaction mechanism in vivo and in vitro. Methods: To establish an in vivo model of sepsis-induced liver injury, rats were treated with high-grade cecal ligation and puncture (CLP). Hematoxylin-eosin staining was applied to observe the liver pathological changes, and liver function was examined using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) assay kits. Enzyme-linked immunosorbent assay (ELISA) kits were employed to assess the levels of inflammatory cytokines in serum and tissues. The activities of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were analyzed using MDA, SOD, and GSH-Px assay kits, respectively. The apoptosis of liver tissues was measured by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) staining, and western blot was employed to estimate apoptosis-related proteins. In vitro, 0.5 µg/mL lipopolysaccharide (LPS) was adopted to administrate primary hepatocytes. The expressions of receptor for advanced glycation end products (RAGE)/p38-related proteins were evaluated by western blot. Cell counting kit-8 (CCK-8) and dichloro-dihydro-fluorescein diacetate (DCFH-DA) assays were utilized to estimate cell viability and reactive oxygen species (ROS) content. Moreover, the transfection efficacy of overexpression (Ov)-RAGE in primary hepatocytes was tested by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Results: IDE could improve liver function and reduce sepsis-induced pathological damage. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the serum and liver tissue of sepsis rats were suppressed by IDE. Additionally, IDE repressed the oxidative stress and apoptosis of liver tissues in sepsis-induced rats. IDE also inhibited RAGE/p38 signaling. Furthermore, IDE revived the decreased viability in LPS-induced hepatocytes concentration-dependently. After overexpressing RAGE, RAGE expression in hepatocytes was significantly elevated. Further functional experiments revealed that IDE attenuated cell viability injury, apoptosis, oxidative stress, and inflammatory damage in LPS-induced hepatocytes via RAGE/p38 signaling. Conclusions: IDE helped to protect against sepsis-induced liver injury via the regulation of RAGE/p38 signaling.

18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(7): 1767-71, 2011 Jul.
Artículo en Zh | MEDLINE | ID: mdl-21942020

RESUMEN

In situ TLC/FTIR technique has tremendous potential in the analysis of complex mixtures. However, the progress in this technique was quite slow. The reason is that conventional stationary phase such as silica gel etc. has strong absorption in FTIR spectrum and thus brings about severe interference in the detection of samples. To solve the problem, the authors propose to use barium fluoride fine particles as stationary phase of TLC plate. The reasons are as follows: Barium fluoride wafer has been extensively used as infrared window in FTIR experiments and it has no absorbance in an IR region between 4 000 and 800 cm'. As a matter of fact, the atomic mass of barium and fluoride is quite large, thus the normal vibration of BaF2 lattice is limited in far-IR region and low frequency part of mid-IR region. Therefore, the interference caused by IR absorption of stationary phase can be resolved if BaF2 is used as stationary phase of TLC plate. Moreover, BaF2 is quite stable and insolvable in water and most organic solvents and it will not be dissolved by mobile phase or react with samples in TLC separation. Additionally, decreasing the particle size of BaF2 is very important in TLC/FTIR analysis technique. The reason is two-fold: First, decreasing the particle size of stationary phase is helpful to improving the efficiency of separation by TLC plate; second, decreasing the size of BaFz particle can improve the quality of FTIR spectra by alleviating the problem of light scattering. By optimizing the synthetic conditions, fine particles of barium fluoride were obtained. SEM results indicate that the size of the BaF2 particles is around 500 nm. FTIR spectrum of the BaF2 particles shows that no absorption of impurity was observed. Moreover, the elevation of baseline caused by light scattering is insignificant. The authors have developed a new technique named "settlement volatilization method" to prepare TLC plate without polymeric adhesive that may bring about significant interference in FTIR analysis. Preliminary TLC experiments proved that the TLC plate using BaF2 fine particles as stationary phase can separate rhodamine B from methylene blue successfully. Applications of barium fluoride fine particles as stationary phase have bright perspective in the development of new in-situ TLC/FTIR analysis techniques.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 248: 119284, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33310617

RESUMEN

A feasible, effective and non-destructive method that could be used to differentiate architectural paints was proposed by Microscopic laser Raman spectroscopy and chemometrics. A total of 252 white architectural paints from 7 different manufacturers were prepared for evaluating the potential of differentiating them. 5th Newton interpolation polynomial combined with Savitzky-Golay 7-point and 1st or 2nd polynomial smoothing under the 1st-order derivative were considered as the optimal pre-processing method for MLRM data. The Bayes discriminant analysis model realized 100% accuracy based on discriminant functions Z1, Z2 and Z3, which was the more useful and practical method for differentiating white architectural paints than that of multilayer perceptron and radial basis function neural network models. All samples were differentiated exactly, which was rapid and non-destructive. The designed method demonstrated the potential of Microscopic Laser Raman spectroscopy in combination with pre-processing and chemometrics as a universal, confirmatory, and accurate method for the white architectural paint differentiation in forensic science.

20.
Ir J Med Sci ; 190(3): 1183-1188, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33094466

RESUMEN

PURPOSE: Vitamin C has shown benefits in patients with sepsis in addition to standard therapy recently. However, further evidence is required to verify the efficacy of vitamin C in clinical practice. This study aimed to investigate the effect of adjunctive intravenous high-dose vitamin C treatment on hospital mortality in patients with sepsis. METHODS: One hundred seventeen patients with sepsis in our department from June 2017 to May 2019 were randomly divided into two groups: the control group (56 cases) and the vitamin C group (61 cases). The control group was treated by the routine and basic therapy with intravenous drip of 5% dextrose and placebo (100 ml/time, 2 times/day), while the vitamin C group was administered intravenously by 3.0 g vitamin C dissolved into 5% dextrose (100 ml/time, 2 times/day) based on the control group. The mortality and efficacy were statistically analyzed and compared between the two groups. RESULTS: The 28-day mortality differed significantly between the control group and the vitamin C group (42.97% vs. 27.93%) (p < 0.05). The changes in the sepsis-related organ failure assessment (ΔSOFA) scores at 72 h after ICU admission (4.2 vs. 2.1), the application time of vasoactive drugs (25.6 vs. 43.8), and the procalcitonin clearance (79.6% vs. 61.3%) differed significantly between groups (p < 0.05). CONCLUSION: The early treatment of sepsis with intravenous high-dose vitamin C in combination with standard therapy showed a beneficial effect on sepsis, in terms of the reduced 28-day mortality, the decreased SOFA score, and the increased clearance rate of procalcitonin.


Asunto(s)
Sepsis , Ácido Ascórbico/uso terapéutico , Humanos , Unidades de Cuidados Intensivos , Polipéptido alfa Relacionado con Calcitonina , Pronóstico , Curva ROC , Estudios Retrospectivos , Sepsis/tratamiento farmacológico
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