T-bet、GATA-3 与T 细胞亚群在再障中的相关性研究

目的:探讨外周血中T-bet和GATA-3 mRNA的表达在再生障碍性贫血中的发病机制及意义。方法:入选27例再障患者,其中重型再障15例,轻型再障l2例,25例健康体检者为对照组。采用流式细胞术检测参试者外周血Thl和Th2细胞,RT-PCR检测外周血单核细胞中转录因子T-bet和GATA-3 mRNA的表达。结果:与健康对照组相比,再障患者血浆T-bet mRNA与Th1细胞比例显著升高(P<0.01),GATA-3 mRNA与Th2细胞明显降低(P<0.05、P<0.01)。与轻型再障患者相比,重型再障患者血浆转录因子T-bet mRNA及Th1细胞比例均明显升高(P<0.01),GATA-3 mRNA水平与Th2细胞比例也显著下降(P<0.05、P<0.01)。结论:T-bet与GATA-3异常表达可增强Th1细胞功能,抑制Th2细胞功能,导致患者免疫功能异常,最终引起再障发生、发展。     

脐带间充质干细胞与再生障碍性贫血

再生障碍性贫血(aplastic anemia,AA)是由于物理、化学、生物或不明因素作用使骨髓造血干细胞和骨髓微环境严重受损,造成骨髓造血功能降低或衰竭,以全血细胞减少为主要表现的一组综合征。间充质干细胞(MSC)是属于中胚层的一类多能干细胞,主要存在于结缔组织和器官间质中。不仅具有多向分化潜能,还有多种免疫调节作用。许多研究表明MSCs抑制同种异体效应T淋巴细胞增殖,还能下调T淋巴细胞表面的活化分子CD25、CD38、CD69的表达。MSCs对DCs的分化、成熟和活化具有抑制作用,改变DCs的细胞因子分泌,使成熟的DCl分泌TNF-a减少,DC2分泌IL-10增加,从而抑制T淋巴细胞增殖。MSCs能够抑制IL-2和IL-15介导的NK细胞增殖,使IL-2刺激NK细胞分泌的IFN-y减少。通过这些机制来干预再生障碍性贫血,同时研究发现MSCs免疫原性较低。尤其脐带MSC,因为其独特优势,目前已经成为干细胞干预治疗AA的研究热点。     

The Effects of Free Radicals on Cobalamin and Iron

The aim of this communication is to show the means by which free radicals could deleteriously alter the metabolism of cobalamin (vitamin B12) and iron in their attempt to protect the body against neoplasia or inflammation and in doing so, create the anaemia of chronic disease.     

Environment change, geographic migration and sickle cell anaemia

The classic model describing the interaction between sickle cell anaemia and malaria is one of the most notable achievements of population genetics. Nevertheless, only panmictic populations in steady environments have been studied theoretically to date. In this paper, environment change and geographic inhomogeneity are introduced. The rate of decrease of mutation after environment improvement is obtained. The kinetics of the spread of disease after the initial mutation, together with the genetic composition profile near the borders of malaria areas, are calculated. The results are compared with the empirical data on the mutation level in African and African-American populations. It is shown that the spread of disease and decrease in mutation are highly asymmetric: the mutation level increases exponentially and decreases much more slowly (as a power function). The mathematical and biological reasons for this behaviour are discussed.     

MHF1 plays Fanconi anaemia complementation group M protein (FANCM)‐dependent and FANCM‐independent roles in DNA repair and homologous recombination in plants

Fanconi anaemia complementation group M protein (FANCM), a component of the human Fanconi anemia pathway, acts as DNA translocase that is essential during the repair of DNA interstrand cross‐links. The DNA‐damage‐binding function of FANCM is strongly enhanced by the histone fold‐containing FANCM‐associated protein MHF1. We identified a single homologue of MHF1 in the genome of Arabidopsis thaliana. Similar to the loss of AtFANCM, the loss of AtMHF1 leads to several meiotic defects, such as chromosome bridges between bivalents and an unequal distribution of chromosomes. Moreover, MHF1, together with FANCM, is involved in interstrand cross‐link repair in plants. This phenotype is detectable only in double mutants of the RecQ helicase and BLM homologue RECQ4A, which appears to function in a parallel pathway to the FANCM/MHF1 complex. However, in somatic cells, FANCM has an MHF1‐independent function in replicative repair in a parallel pathway to the endonuclease MUS81. Furthermore, MHF1 is required for efficient somatic homologous recombination (HR) – a role antagonistic to FANCM. FANCM and RECQ4A define two parallel pathways of HR suppression in Arabidopsis. Hyperrecombination in the fancm but not the recq4A mutant can be abolished by MHF1 mutations. This finding indicates that MHF1 and FANCM act at different steps of a single, common, HR pathway.     

Mechanisms of 8‐aminoquinoline induced haemolytic toxicity in a G6PDd humanized mouse model

Primaquine (PQ) and Tafenoquine (TQ) are clinically important 8‐aminoquinolines (8‐AQ) used for radical cure treatment of P. vivax infection, known to target hepatic hypnozoites. 8‐AQs can trigger haemolytic anaemia in individuals with glucose‐6‐phosphate dehydrogenase deficiency (G6PDd), yet the mechanisms of haemolytic toxicity remain unknown. To address this issue, we used a humanized mouse model known to predict haemolytic toxicity responses in G6PDd human red blood cells (huRBCs). To evaluate the markers of eryptosis, huRBCs were isolated from mice 24–48 h post‐treatment and analysed for effects on phosphatidylserine (PS), intracellular reactive oxygen species (ROS) and autofluorescence. Urinalysis was performed to evaluate the occurrence of intravascular and extravascular haemolysis. Spleen and liver tissue harvested at 24 h and 5–7 days post‐treatment were stained for the presence of CD169+ macrophages, F4/80+ macrophages, Ter119+ mouse RBCs, glycophorin A+ huRBCs and murine reticulocytes (muRetics). G6PDd‐huRBCs from PQ/TQ treated mice showed increased markers for eryptosis as early as 24 h post‐treatment. This coincided with an early rise in levels of muRetics. Urinalysis revealed concurrent intravascular and extravascular haemolysis in response to PQ/TQ. Splenic CD169+ macrophages, present in all groups at day 1 post‐dosing were eliminated by days 5–7 in PQ/TQ treated mice only, while liver F4/80 macrophages and iron deposits increased. Collectively, our data suggest 8‐AQ treated G6PDd‐huRBCs have early physiological responses to treatment, including increased markers for eryptosis indicative of oxidative stress, resulting in extramedullary haematopoiesis and loss of splenic CD169+ macrophages, prompting the liver to act as the primary site of clearance.     

Nitric oxide and changes of iron metabolism in exercise

Accumulated data imply that exercise itself might not lead to a true iron deficiency or 'sport anaemia' in a healthy athlete who has adequate iron intake. The higher prevalence of iron deficiency anaemia in younger female athletes might be not due to exercise itself, but probably results from dietary choices, inadequate iron intake and menstruation. These factors can also induce iron deficiency or anaemia in the general population. However, exercise does affect iron metabolism, leading to low or sub-optimal iron status. The underlying mechanism is unknown. In this review, recent advances in the study of the effect of exercise on iron metabolism and nitric oxide, and the relationship between nitric oxide and iron status in exercise are discussed. A hypothesis that increased production of nitric oxide might contribute to sub-optimal iron status in exercise is proposed.