Research progress on application of machine perfusion in quality maintenance of donor kidney from organ donation after citizen's death / 器官移植

Organ donation after citizen's death has become the main source of organ donation in China. However, the complexity of donor quality and the increasing proportion of expanded criteria donor (ECD) exert significant impact upon the availability of donor kidney and the long-term prognosis of recipients after kidney transplantation. Strengthening the quality maintenance and evaluation of donor kidney is of great significance for improving the quality of donor kidney, increasing the procurement and utilization of donor kidney and prolonging the long-term survival of recipients and kidney allografts. As one of the major approaches of organ preservation, machine perfusion preservation may not only prolong the preservation time and improve the quality of donor kidney, but also play a critical role in the repair and function evaluation of donor kidney. Based on literature review, several hot issues, corresponding treatment strategies and research progress on machine perfusion in the quality maintenance of donor kidney from organ donation after citizen's death were reviewed in this article, aiming to provide reference for selecting the optimal preservation method of donor kidney and enhancing the quality and utilization rate of ECD donor kidney.

Effect of Celastrol Based on IRAK4/ERK/p38 Signaling Pathway on Proliferation and Apoptosis of Multiple Myeloma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. @*METHODS@#CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. @*RESULTS@#Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). @*CONCLUSION@#Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.

Discovery of the ARP2 protein as a determining molecule in tumor cell death

Cancer is a multifactorial disease that constitutes a serious public health problem worldwide. Prostate cancer advanced stages are associated with the development of androgen-independent tumors and an apoptosis-resistant phenotype that progresses to metastasis. By studying androgen-independent lymphoid nodule carcinoma of the prostate (LNCaP) cells induced to apoptosis by serum elimination, we identified the activation of a non-selective cationic channel of 23pS conductance that promotes incoming Ca2+ currents, as well as apoptosis final stages. arp2cDNA was isolated and identified to be of the same cell type, and mRNA was expressed in Xenopus laevis oocytes, which was found to be associated with the activation of incoming Ca2+ currents and induction to apoptosis. cDNA, which encodes the ARP2 protein, was overexpressed in LNCaP cells and Chinese hamster ovary cells, which induced apoptosis. Our evidence suggests that protein ARP2 overexpression and transit to the cell membrane allows an increased Ca2+ incoming current that initiates the apoptosis process in epithelial-type cells whose phenotype shows resistance to programmed cell death.

Rol del laboratorio en el diagnóstico del hiperaldosteronismo primario / Laboratory Role in the Diagnosis of Primary Aldosteronism

El aldosteronismo primario se considera actualmente el causante de un 8 a 12 % de los casos de hipertensión arterial. El aumento de su prevalencia es consecuencia de cambios en los criterios diagnósticos. El tamizaje inicial se realiza en el laboratorio determinando la relación aldosterona/actividad de renina plasmática, para lo que se requieren estrictas condiciones preanalíticas; condiciones de reposo o deambulación, evitando interferencias de drogas terapéuticas que pueden afectar el resultado, de obtención y de conservación de la muestra, entre otras. Debido a la alta variabilidad en la medición de la actividad de renina plasmática, (radioinmunoensayo operador dependiente), se está proponiendo el uso de la relación aldosterona/concentración de renina, (donde la concentración de renina se determina por un método automatizado) aunque aún no hay consenso. El método de tamizaje es fundamental para el inicio del estudio de un paciente e influye en la prevalencia actual. Una vez establecidos los valores de corte para cada laboratorio, los pacientes con tamizajes positivos deben ser sometidos a pruebas confirmatorias, por ejemplo sobrecarga con sodio, o supresión con fludrocortisona, para evidenciar la secreción autónoma de aldosterona. Una vez confirmada se debe diferenciar la causa; las principales son adenoma productor de aldosterona e hiperplasia adrenal bilateral. El diagnóstico temprano permite el tratamiento correcto, evitando comorbilidades causadas por la hipertensión arterial (HTA) y remodelaciones vasculares y cardíacas por el exceso de aldosterona. Los tratamientos clásicos para la HTA no siempre son de utilidad en el aldosteronismo primario, por ello es importante el diagnóstico de la patología.

Primary aldosteronism is nowadays considered the cause of 8 to 12 % cases of hypertension. The increase in its prevalence is due to changes in diagnostic criteria. Initial screening is performed in the laboratory by obtaining the aldosterone to plasma renin activity ratio, for which strict preanalytical conditions are required, including; supine or upright posture; interaction of therapeutic drugs which may alter results; sample extraction and conservation, among others. Given the high variability in the measurement of plasma renin activity and its complexity (RIA), the use of the aldosterone to renin concentration ratio is proposed (where renin concentration is determined by an automated immunoassay), although no consensus has been reached in this matter. The screening method is essential to primarily identify those patients who should be further studied, and it influences the statistics on actual prevalence of primary aldosteronism. Once cutoff values have been determined for each laboratory, patients with positive screening results must be further submitted for confirmation tests, such as salt-loading test or fludrocortisone suppression test, in which the autonomous secretion of aldosterone is confirmed. Then, the cause of the excessive aldosterone production must be determined. The most common are aldosterone producing adenoma and bilateral adrenal hyperplasia. Early diagnosis allows for the correct treatment, minimizing comorbidities caused by hypertension and by vascular and cardiac remodelation due to the excess of aldosterone. Classic treatment for hypertension is not always useful in patients with primary aldosteronism; this is why it is important to know how to diagnose the underlying pathology.

Viral exploitation of actin:force-generation and scaffolding functions in viral infection / 中国病毒学·英文版

As a fundamental component of the host cellular cytoskeleton, actin is routinely engaged by infecting viruses. Furthermore, viruses from diverse groups, and infecting diverse hosts, have convergently evolved an array of mechanisms for manipulating the actin cytoskeleton for efifcacious infection. An ongoing chorus of research now indicates that the actin cytoskeleton is critical for viral replication at many stages of the viral life cycle, including binding, entry, nuclear localization, genomic transcription and reverse transcription, assembly, and egress/dissemination. Speciifcally, viruses subvert the force-generating and macromolecular scaffolding properties of the actin cytoskeleton to propel viral surifng, internalization, and migration within the cell. Additionally, viruses utilize the actin cytoskeleton to support and organize assembly sites, and eject budding virions for cell-to-cell transmission. It is the purpose of this review to provide an overview of current research, focusing on the various mechanisms and themes of virus-mediated actin modulation described therein.

p41-Arc, a regulatory subunit of Arp2/3 complex, can induce premature senescence in the absence of p53 and Rb

Cellular senescence is a tumor-suppressive process instigated by proliferation in the absence of telomere replication, by cellular stresses such as oncogene activation, or by activation of the tumor suppressor proteins, such as Rb or p53. This process is characterized by an irreversible cell cycle exit, a unique morphology, and expression of senescence-associated-beta-galactosidase (SA-beta-gal). Despite the potential biological importance of cellular senescence, little is known of the mechanisms leading to the senescent phenotype. p41-Arc has been known to be a putative regulatory component of the mammalian Arp2/3 complex, which is required for the formation of branched networks of actin filaments at the cell cortex. In this study, we demonstrate that p41-Arc can induce senescent phenotypes when it is overexpressed in human tumor cell line, SaOs-2, which is deficient in p53 and Rb tumor suppressor genes, implying that p41 can induce senescence in a p53-independent way. p41-Arc overexpression causes a change in actin filaments, accumulating actin filaments in nuclei. Therefore, these results imply that a change in actin filament can trigger an intrinsic senescence program in the absence of p53 and Rb tumor suppressor genes.

Actin-interacting and flagellar proteins in Leishmania spp: bioinformatics predictions to functional assignments in phagosome formation

Several motile processes are responsible for the movement of proteins into and within the flagellar membrane, but little is known about the process by which specific proteins (either actin-associated or not) are targeted to protozoan flagellar membranes. Actin is a major cytoskeleton protein, while polymerization and depolymerization of parasite actin and actin-interacting proteins (AIPs) during both processes of motility and host cell entry might be key events for successful infection. For a better understanding the eukaryotic flagellar dynamics, we have surveyed genomes, transcriptomes and proteomes of pathogenic Leishmania spp. to identify pertinent genes/proteins and to build in silico models to properly address their putative roles in trypanosomatid virulence. In a search for AIPs involved in flagellar activities, we applied computational biology and proteomic tools to infer from the biological meaning of coronins and Arp2/3, two important elements in phagosome formation after parasite phagocytosis by macrophages. Results presented here provide the first report of Leishmania coronin and Arp2/3 as flagellar proteins that also might be involved in phagosome formation through actin polymerization within the flagellar environment. This is an issue worthy of further in vitro examination that remains now as a direct, positive bioinformatics-derived inference to be presented.

Preparation of replication-deficient recombinant adenovirus coding ARP2 gene / 中国实用内科杂志

Objective To construct the replication-deficient recombinant adenovirus coding ARP2 gene before the studies of gene transfection to ischemic myocardium.Methods From Dec.2004 to Oct.2005,in the Department of Cardiology,Changhai Hospital of the Second Military Medical Univesity,the ARP2-pAxCAwt was constructed by inserting the cDNA of interest into the SwaI site of pAxCAwt.Results The right direction of the insert was confirmed by restriction.Conclusion The direction of the insert must be confirmed by restriction analysis,and the DNA package protein is much helpful during the transfection of the recombinant cosmid to E.coli.

Diagnóstico de las condiciones de trabajo y salud ocupacional del sector informal manufacturero en Santa Fe de Bogotá / Diagnosis of working conditions and occupational health in the informal manufacturing sector in Santa Fe de Bogota

Investigación por demanda dentro de la línea de salud Pública. El proyecto toma como unidad de análisis la empresa. Sus objetivos generales son: contribuir al estudio de la informalidad y sus efectos en los trabajadores, las empresas y los países ubicar la investigación dentro de tres marcos de referencia: a) la informalidad, b) la salud ocupacional y c) la perspectiva de género, incluyendo en los tres el punto de vista global (países con un grado de desarrollo similar a Colombia), el análisis nacional y el caso específico de Santa Fe de Bogotá; identificar las condiciones de trabajo dadas por el entorno socioeconómico, el ambiente físico, químico y biológico del sitio de trabajo, la organización del trabajo y la relación entre el trabajador y los elementos de trabajo; documentar las condiciones de salud ocupacional de los trabajadores en el sector manufacturero y en las industrias de producción de alimentos, fabricación de prendas de vestir, productos metálicos y muebles; ofrecer sugerencias que puedan usarse para remediar las condiciones de salud ocupacional observadas. Los objetivos específicos fueron los siguientes: identificar las características de los trabajadores del sector informal en las industrias estudiadas (edad, nivel socioeconómico, sexo, educación); identificar las condiciones de trabajo del sector informal relacionadas con aspectos ambientales, tales como ruido, contaminación con productos químicos o biológicos, iluminación, exposición a temperaturas extremas y condiciones ergonómicas; observar los procesos de trabajo; identificar los problemas de salud de cada una de las industrias estudiadas mediante exámenes médicos, pruebas de laboratorio y entrevistas a profundidad e historias de vida del trabajador y de la empresa; sugerir modelos de intervención de salud ocupacional adecuados a cada índustria y empresa; recomendar un modelo de seguimiento permanente que asegure la aplicación de las normas que se dictaron para cada caso en el proyecto. Estas recomendaciones servirán a trabajadores, empresarios y entidades responsables de la salud ocupacional de los trabajadores.

Research on demand within the line of public health. The project takes the company as the unit of analysis. Its general objectives are: to contribute to the study of informality and its effects on workers, companies and countries to place the research within three frames of reference: (a) informality, (b) occupational health and (c) the gender perspective, including in all three the global point of view (countries with a degree of development similar to Colombia), the national analysis and the specific case of Santa Fe de Bogotá; identify the working conditions given by the socioeconomic environment, the physical, chemical and biological environment of the work site, the organization of work and the relationship between the worker and the work elements; to document the occupational health conditions of workers in the manufacturing sector and in the food production, garment manufacturing, metal products and furniture industries; to offer suggestions that can be used to remedy the occupational health conditions observed. The specific objectives were the following: identify the characteristics of informal sector workers in the industries studied (age, socioeconomic level, sex, education); identify informal sector working conditions related to environmental aspects, such as noise, contamination with chemical or biological products, lighting, exposure to extreme temperatures, and ergonomic conditions; observe work processes; identify the health problems in each of the industries studied through medical examinations, laboratory tests and in-depth interviews and life histories of the worker and the company; suggest occupational health intervention models appropriate to each industry and company; recommend a permanent follow-up model to ensure the application of the norms that were dictated for each case in the project. These recommendations will be useful to workers, employers and entities responsible for the occupational health of workers.