Angiotensin I-converting enzyme is expressed by erythropoietic cells of normal and myeloproliferative bone marrow

It is proposed that a locally active, intrinsic renin-angiotensin system (RAS) exists in the bone marrow (BM) and plays a role in regulating haematopoiesis. Angiotensin II type I receptor has been detected on erythroid burst-forming unit-derived cells; its antagonist losartan and angiotensin I-converting enzyme (ACE) inhibitors can suppress erythropoiesis. The possible role of ACE/RAS in BM was investigated by evaluating ACE expression in normal BM, several myeloproliferative disorders and myelodysplasia. Immunohistochemical studies showed that erythroid elements expressed ACE protein in both normal and disturbed haematopoiesis. The presence of ACE in erythroid cells suggests another mechanism for direct ACE inhibitor activity in erythropoiesis.     

Low expression of the putative tumour suppressor gene gravin in chronic myeloid leukaemia, myelodysplastic syndromes and acute myeloid leukaemia

The putative tumour suppressor gene gravin is down-regulated in several solid tumours and is implicated in tumorigenesis. We have evaluated the expression levels of the gravin gene in the CD34(+)/blast cells of a range of myeloid malignancies as compared with controls using real-time quantitative polymerase chain reaction (PCR). Gravin was markedly down-regulated in 41 of 41 patients with acute myeloid leukaemia (AML), nine of 10 patients with myelodysplastic syndromes (MDS) and 33 of 33 patients with chronic myeloid leukaemia (CML), of whom 24 were in blast crisis (BC). We have shown that gravin is consistently down-regulated in the CD34(+)/blast cells of myeloid malignancies and may play a role in the molecular pathogenesis of these disorders.     

慢性乙型肝炎患者外周血单个核细胞基质金属蛋白酶-1及其抑制因子基因的表达

目的 比较外周血单个核细胞(PBMC)及自身血清中基质金属蛋白酶-1(MMP-1)及金属蛋白酶组织抑制因子-1(TIMP-1)表达水平,探讨MMP-1及TIMP-1基因表达对肝纤维化的诊断价值.方法 实时荧光定量反转录聚合酶链反应(FQ-RT-PCR)方法分别检测37例慢性乙型肝炎患者及20例健康对照者PBMC中MMP-1及TIMP-1 mRNA的表达水平,双抗体央心酶联免疫吸附方法检测血清MMP-1及TIMI-1水平;慢性乙型肝炎患者均行肝组织穿刺活检,行纤维化程度分期(S).组间比较采用多个独立样本非参数检验,并作Spearman相关性分析.结果 健康对照组PBMC中MMP-1 mRNA及TIMP-1 mRNA呈低水平表达,慢性乙型肝炎患者PBMC中MMP-1mRNA表达水平与健康对照组比较差异无统计学意义,而TIMP-1 mRNA表达水平显著高于健康对照组的(0.48±0.80)lg拷贝/μL,血清TIMP-1也高于健康对照组的(158.29±58.58)μg/L.随着慢性乙型肝炎肝纤维化程度加重,各期之间MMP-1 mRNA的表达水平及血清MMP-1水平比较差异无统计学意义(χ~2=8.960,P=0.111;χ~2=7.898,P=0.211);从S1～S4,TIMP-1 mRNA表达水平依次为(1.67±0.84)、(3.48±2.08)、(5.86±3.47)及(8.14±6.48)lg拷贝/μL,血清TIMP-1水平依次为(233.73±64.84)、(262.10μ71.12)、(301.15μ62.74)及(381.15±152.75)μg/L,各期之间TIMP-1mRNA表达水平及血清TIMP-1水平比较差异均有统计学意义(χ~2=14.290,P=0.002;χ~2=12.209,P=0.007).PBMC中TIMI-1 mRNA、血清TIMP-1与肝纤维化呈正相关(r=0.752.P<0.01;r=0.530,P=0.008).结论 PBMC中TIMP-1 mRNA表达水平及血清TIMP-1水平与肝脏纤维化程度密切相关.PBMC中TIMP-1 mRNA及血清TIMP-1可以作为诊断肝纤维化的新指标,尤其PBMC中TIMP-1 mRNA诊断价值最大.     

Increased peripheral RORα and RORγt mRNA expression is associated with acute‐on‐chronic hepatitis B liver failure

Summary. T helper cells17 (Th17) have accurate but inconclusive roles in the pathogenesis of acute‐on‐chronic hepatitis B liver failure (ACHBLF). Retinoic acid‐related orphan receptor γ t(RORγt) and RORα are two lineage‐specific nuclear receptors directly mediating Th17 differentiation. This study was aimed to evaluate the gene expression of RORα and RORγt and their potential role in ACHBLF. Forty patients with liver failure, 30 with chronic hepatitis B (CHB) and 20 healthy controls were studied. The mRNA levels of RORα and RORγt in peripheral mononuclear cells were determined by quantitative real‐time polymerase chain reaction. The frequency of peripheral Th17 cells was determined using flow cytometry. The serum levels of interleukin‐6(IL‐6), transforming growth factor –β (TGF‐β), interleukin‐17(IL‐17), interleukin‐23(IL‐23) and interferon‐γ (IFN‐γ) were measured by enzyme‐linked immunosorbent assay. The frequency of peripheral Th17 cells in patients with liver failure was significantly increased compared to patients with CHB and controls. The peripheral mRNA levels of RORα and RORγt in hepatitis B‐associated acute‐on‐chronic liver failure were significantly higher than in patients with CHB and controls as were the serum levels of IL‐6 and TGF‐β. The serum level of IFN‐γ in patients with acute‐on‐chronic liver failure from HBV was significantly higher than patients with CHB but lower than controls. In patients with acute‐on‐chronic liver failure associated with HBV, RORγt, IL‐6 and IL‐23 were positively correlated with the frequency of Th17 cells, while RORα, TGF‐β and IFN‐γ had no correlation with the latter. The mRNA level of RORγt was positively correlated with model of end‐stage liver disease (MELD) score, but there was no correlation of RORα and MELD score. RORγt plays an important role in the pathogenesis of acute‐on‐chronic HBV‐associated liver failure and might be considered to be a candidate factor consistent with the severity of disease.