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Wnt/β-catenin is an evolutionarily conserved, complex developmental signal pathway that regulates embryogenesis, cell fate, tissue homeostasis, injury repair, and the pathogenesis of human diseases. Mounting evidence demonstrates that Wnt/β-catenin signaling plays a key role in early nephrogenesis. It is relatively silent in normal adult kidneys but reactivated in a wide variety of animal models of nephropathies and in human kidney diseases. Activation of Wnt/β-catenin after acute kidney injury contributes to proper repair and regeneration of damaged renal tubules. However, sustained activation of this signal cascade is closely related to the development and progression of fibrotic chronic kidney disease. In this paper, we systematically review the components and mechanisms of Wnt/β-catenin signaling and its role in kidney repair and fibrosis after injury. A better delineation of the mechanisms of this pathway will provide novel targets and new strategies for designing effective treatment of various kidney diseases.
Assuntos
Animais , Humanos , Fibrose , Rim/metabolismo , Insuficiência Renal Crônica , Via de Sinalização Wnt , beta Catenina/metabolismoRESUMO
Objective:To understand the current status of the evidence-based practice program of physical restraint in ICU patients and analyze its influencing factors, formulate and implement an action plan for continuous application of the program, so as to improve the knowledge level and evidence-based nursing ability of nurses, promote the improvement of patient outcomes, and strengthen the organization′s evidence-based cultural atmosphere.Methods:This study selected the program application departments of China Japan Friendship Hospital Surgical ICU as the research object, including all nurses, patients, nursing process, department standard system, etc. To understand the status and influencing factors of the project through observation and interview methods. The "Optimized Version of Evidence-based Practice Program of Physical Restraint in ICU Patients" was formulated and implemented, and a before-and-after comparative study method was used to comprehensively evaluate the implementation effect from the level of patients, nurses and organization.Results:The implementation rate of the 7 review standards of the program application department showed a downward trend; the patient restraint rate and restraint duration increased compared with the previous period; after the implementation of the optimized version program, the implementation of each item had been improved; the physical restraint rate decreased from 34.91% (37/106) before optimization to 28.57% (8/28) ( χ 2 value was 0.40, P>0.05), and the time of physical restraint decreased from 60.93 hours before optimization to 48.09 hours after optimization ( Z value was -0.19, P>0.05). Conclusions:The continuous application of the evidence-based practice project of physical restraint in ICU patients was not very optimistic. The continuity of implementation was affected by many factors. The continuous quality improvement of this evidence-based practice project can promote the improvement of the standard of physical restraint of patients, improve the quality of life of patients, promote the improvement of nurses' knowledge level and the improvement of evidence-based nursing ability; at the same time, it created a better organization′s evidence-based cultural atmosphere.
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Our previous study showed that malignant phenotype of human promyelocytic leukemia cells could he suppressed by fusion of them with mouse reticulocytes. In order to investigate the morphological changes for malignancy reversion, the present experiment was designed to study the microscepic and submicroscopic structure of cybrid cells and compared with their parental tumor cells. The results indicated that during the short period of cybrid cell cultivation, nuclei of numerous cybrid cells became pyknotic and eccentric, and some cells showed the process of nuclear expulsion (denucleation). The cybrids which cultivated for long period in vitro developed into more mature cells along both myeloid and erythroid differentiation pathway. The effects of mouse reticulocyte cytoplasmic factor on differentiation pathway of human promyelocytic leukemia cells were discussed.
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The heterospecies hybrid cells(HL-N)from the fusion of human promyelocy-tic leukemia mutant cells(HL-60-AR)and mouse bone marrow nucleated red cellswere established in HAT selective medium.Malignant phenotype comparative analy-sis between parental tumor cells and hybrid cells showed that growth ability ofhybrid cells was decreased.The hybrid cells reduced their DNA synthesis rate andlost the ability of colony-forming in 0.3% soft agar medium.The cells lost tumor-producing ability when they were transplanted into nude mice also.Inhibition orreduction of c-myc oncogene expression was demonstrated by Northern molecularhybridization techniques.The ultrastructure of hybrid cells were also different fromtheir parental cells.These results mentioned above showed that the mouse bone mar-row nucleated red cells might provide some peculiar factors(both nuclear factorsand cytoplasmic factors)to inhibit the expression of HL-60-AR cell malignant phe-notypes.
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The present study is designed to establish a xenograft model of human promyelocytic leukemia cell mutant (HL-60-AR) deficient in hypoxanthine guanine phosphoribosyltransferase (HGPRT) in nude mice. A solid leukemia sarcoma developed after subcutaneous inoculation with HL-60-AR cells. Comparative studies of HL-60-AR/Nu tumor cells in nude mice and cultured HL-60-AR cells in vitro revealed virtual identity as shown by light microscopic morphology, ultrastructure of cell, cytochemistry, chromosome analysis, LDH isoenzyme pattern, genetic markers and differentiated characters assay. Up to now, twelve generations haw been transmitted in rive by inoculating with the solid tumor Cells developed in nude mice. This nude mice model in which human leukemia cells grew could be considered as a useful model for in rive studies of human leukemic cells proliferation, differentiation and the screening for anti-leukemia drugs.
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The fine ultrastructure and localization of acid phosphatase in cell ultrastructuralevel of a HGPRT-human promyelocytic leukemia cell mutant(HL-60-AR)arestudied by scanning electron microscopy,transmission electron microscopy,freezeetching,and electron microscopic cytochemistry techniques.The results of theobservation show that the ultrastructural characteristics of HL-60-AR cells aresimilar to that of HL-60 cells.There are microvilli and ridges over cell surface.Thecells have large nucleus with prominent nucleoli,and numerous nuclear pores.Thereare less developed Golgi complex,expanded rough endoplasmic reticulum andabundant polyribosomes.After treatment with retinoic acid(RA)at 10~(-6) mol/L for 5days,HL-60-AR cells differentiate along myeloid pathway and have a decreasednucleocytoplasmic ratio accompanied with nuclear condensation and segmention.A (?)ignificant increase of specific granules is demonstrated.Microvilli of the cellsdisappear,surface features of the treated cells become more irregular and largeprotrusion and blunt pseudopodia appear.Increase of acid phosphatase content localizedon azurophilic granules(lysosomes)and Golgi complex is showed.The application offour kinds of electron microscopic techniques might provide the best way foridentifying cell ultrastructure.