不同类型干细胞在心肌组织工程中的应用及进展

慢性缺血性心脏病多由冠状动脉粥样硬化引起,目前治疗上较为棘手.近年来,心肌组织工程的发展为此疾病的治疗带来了曙光.心肌组织工程主要包括种子细胞的获取、支架材料的研制、以及心肌组织的构建三部分.种子细胞的来源和种类则是心肌组织工程中的关键环节.我们总结近年来干细胞研究的进展,对研究较多的几种干细胞在心肌组织工程中的应用作一综述,这些干细胞包括:心脏祖细胞,胚胎干细胞,间充质干细胞,诱导多能干细胞,以及用于构建心肌再生的内皮祖细胞等,并对未来干细胞的发展作一展望.     

Melanotic neuroectodermal tumor of infancy in the soft tissue of the forearm: report of a case

Melanotic neuroectodermal tumor of infancy is rare. Only 3 cases have been reported in the soft tissue of the extremities up to date. It has a typically biphasic feature in morphology. Epithelial and melanotic markers are positive in the epitheliod cells and neuron-specific enolase or synaptophysin is positive in the small blue round cells in immunohistochemistry. Radical resection and close follow-up is the treatment strategy in general situation. Here we report one case of MNTI in the upper extremity with review of the literature. This is the first case of MNTI in the forearm.     

Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects

Aims/hypothesis We examined whether short-term treatment with a thiazolidinedione improves insulin sensitivity in non-obese but insulin-resistant subjects and whether this is associated with an improvement in dysregulated adipose tissue (reduced expression of IRS-1, GLUT4, PPAR co-activator 1 and markers of terminal differentiation) that we have previously documented to be associated with insulin resistance.Methods Ten non-diabetic subjects, identified as having low IRS-1 and GLUT-4 protein in adipose cells as markers of insulin resistance, underwent 3 weeks of treatment with pioglitazone. The euglycaemic–hyperinsulinaemic clamp technique was used to measure insulin sensitivity before and after treatment. Serum samples were analysed for glucose, insulin, lipids, total and high-molecular-weight (HMW) adiponectin levels. Biopsies from abdominal subcutaneous adipose tissue were taken, cell size measured, mRNA and protein extracted and quantified using real-time RT-PCR and Western blot.Results Insulin sensitivity was improved after 3 weeks treatment and circulating total as well as HMW adiponectin increased in all subjects, while no effect was seen on serum lipids. In the adipose cells, gene and protein expression of IRS-1 and PPAR co-activator 1 remained unchanged, while adiponectin, adipocyte P 2, uncoupling protein 2, GLUT4 and liver X receptor- increased. Insulin-stimulated tyrosine phosphorylation and p-ser-PKB/Akt increased, while no significant effect of thiazolidinedione treatment was seen on the inflammatory status of the adipose tissue in these non-obese subjects.Conclusions/interpretation Short-term treatment with pioglitazone improved insulin sensitivity in the absence of any changes in circulating NEFA or lipid levels. Several markers of adipose cell differentiation, previously shown to be reduced in insulin resistance, were augmented, supporting the concept that insulin resistance in these individuals is associated with impaired terminal differentiation of the adipose cells.     

Prevalence of hepatitis C virus infection in B-cell non-Hodgkin's lymphoma: systematic review and meta-analysis

BACKGROUND & AIMS: The aim of our study was to conduct a systematic review of studies evaluating prevalence of hepatitis C virus (HCV) infection in B-cell non-Hodgkin's lymphoma (B-NHL) and to perform a meta-analysis of case-control studies comparing this prevalence with that of a reference group. METHODS: Data sources: Electronic databases and the Cochrane Controlled Trials Register. Study selection: Studies evaluating prevalence of HCV infection in patients with B-NHL. Studies comparing HCV prevalence in B-NHL (cases) and in a reference group (controls) were included in the meta-analysis. Data extraction: Author/country, diagnostic method (serology/PCR), control type, matching/design, and VHC prevalence. Data synthesis: Prevalence of HCV infection and meta-analysis combining the odds ratios (OR). RESULTS: Forty-eight studies (5542 patients) were identified. Mean HCV infection prevalence was 13% (95% CI: 12%-14%), which was higher in Italy (20%) and Japan (14%). Ten studies compared HCV prevalence in B-NHL (17%) and healthy controls (1.5%) (OR: 10.8; 95% CI: 7.4-16), results being homogeneous; OR increased up to 14.1 when only Italian studies were considered. Sixteen studies compared HCV prevalence in B-NHL (13%) and in other hematologic malignancies (2.9%) (OR: 4.2; 95% CI: 2.5-7), also with homogeneous results; OR increased up to 7.8 when subanalysis included only Italian studies. CONCLUSIONS: HCV prevalence in patients with B-NHL is approximately 15%, higher than that reported not only in general population (1.5%) but also in patients with other hematologic malignancies (2.9%), suggesting a role of HCV in the etiology of B-NHL. The striking geographic variation in this association suggests that genetic and/or environmental factors are also involved in the pathogenesis of this disorder.     

芹菜素对链脲佐菌素诱导糖尿病大鼠肝损伤的影响

目的：探讨芹菜素对糖尿病大鼠肝脏的保护作用。方法将大鼠按随机数字表法分为正常对照组,模型组,芹菜素5、10、20和40 mg/kg治疗组。除正常对照组外,其余各组大鼠采用腹腔注射链脲佐菌素（STZ）的方法建立大鼠糖尿病模型。造模成功后,芹菜素5、10、20和40 mg/kg治疗组大鼠腹腔注射相应浓度的芹菜素溶液,正常对照组和模型组腹腔注射等体积生理盐水,1 d/次。连续给药4周后,测定各组大鼠体质量、肝脏/体质量比;采用 HE 染色方法观察各组大鼠肝组织病理学改变;测定血清谷氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和乳酸脱氢酶（LDH）水平;检测肝组织超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）活性及丙二醛（MDA）水平。结果与模型组比较,芹菜素10、20和40 mg/kg治疗组体质量[(261.3±15.8)g、(274.2±18.4)g、(265.9±19.0)g比(250.8±21.4)g]显著增高（P＜0.05或P＜0.01）,肝脏/体质量比[(27.7±5.69)、(26.2±4.91)、(27.3±4.58)比(32.9±5.85)]显著降低（P＜0.05或 P＜0.01）,肝组织病理学改变明显改善;芹菜素5、10、20和40 mg/kg治疗组血清ALT水平[(1039.3±453.9)U/L、(917.6±445.2)U/L、(828.4±309.5)U/L、(721.7±318.3)U/L比(1205.2±484.1)U/L]、AST水平[(97.8±23.8)U/L、(90.1±19.6)U/L、(81.7±15.7)U/L、(86.4±19.2)U/L比(105.3±25.7)U/L]、LDH水平[(983.7±192.6)U/L、(918.3±212.9)U/L、(830.4±174.2)U/L、(871.8±183.1)U/L比(1102.8±211.6)U/L]均较模型组显著降低(P＜0.05或P＜0.01);芹菜素10、20和40 mg/kg治疗组肝组织中SOD[(10.5±1.9)U/mg、(11.6±2.1)U/mg、(10.5±2.0)U/mg 比(9.1±1.8)U/mg]、GSH-Px[(14.2±2.7)U/mg、(15.3±2.9)U/mg、(14.6±2.6)U/mg 比(12.9±2.3)U/mg],CAT[(3.15±0.90)U/mg、(3.58±0.88)U/mg、(3.31±1.09)U/mg比(2.58±0.79)U/mg]活性较模型组升高(P＜0.05或 P＜0.01),MDA 水平[(5.03±1.70)nmol/mg、(4.66±1.51)nmol/mg、(4.73±1.65)nmol/mg 比(5.98±1.62)nmol/mg]较模型组降低(P＜0.05或 P＜0.01)。结论芹菜素具有抗氧化酶活性,可降低自由基损伤,保护糖尿病大鼠肝组织。     

Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat

Aims/hypothesis The adipokine adiponectin has insulin-sensitising, anti-atherogenic and anti-inflammatory properties. Recently, the genes for mouse and human adiponectin receptor-1 (ADIPOR1) and -2 (ADIPOR2) have been cloned. The aim of this study was to investigate whether genetic variants of the genes encoding ADIPOR1 and ADIPOR2 play a role in human metabolism.Materials and methods We screened ADIPOR1 and ADIPOR2 for polymorphisms and determined their association with glucose metabolism, lipid metabolism, an atherogenic lipid profile and inflammatory markers in 502 non-diabetic subjects. A subgroup participated in a longitudinal study; these subjects received diet counselling and increased their physical activity.Results We identified six variants of ADIPOR1 and seven variants of ADIPOR2. A single-nucleotide polymorphism (SNP) in the putative promoter region 8503 bp upstream of the translational start codon (–8503 G/A) of ADIPOR1 (frequency of allele A=0.31) was in almost complete linkage disequilibrium with another SNP (–1927 T/C) in intron 1. Subjects carrying the –8503 A and –1927 C alleles had lower insulin sensitivity, as estimated from a 75 g OGTT (p=0.04) and determined during a euglycaemic clamp (n=295, p=0.04); they also had higher HbA₁c levels (p=0.02) and, although the difference was not statistically significant, higher liver fat (n=85, determined by proton magnetic resonance spectroscopy, p=0.056) (all p values are adjusted for age, sex and percentage of body fat). In the longitudinal study (n=45), the –8503 A and –1927 C alleles were associated with lower insulin sensitivity (p=0.03) and higher liver fat (p=0.02) at follow-up compared with the –8503 G and –1927 T alleles, independently of basal measurements, sex and baseline and follow-up percentage of body fat.Conclusions/interpretation The present findings suggest that the –8503 G/A SNP in the promoter or the –1927 T/C SNP in intron 1 of ADIPOR1 may affect insulin sensitivity and liver fat in humans.Electronic Supplementary Material Supplementary material is available for this article at .     

穗花杉双黄酮在大鼠体内的组织分布研究

目的:建立一种穗花杉双黄酮在大鼠心、肝、脾、肺、肾、脑、胃、大肠、小肠等组织中的分析方法,并考察大鼠灌服穗花杉双黄酮后在各组织中的分布特性。方法:采用HPLC-UV法测定穗花杉双黄酮在大鼠各组织中的含量。按500 mg·kg-1的剂量灌胃给予大鼠穗花杉双黄酮,分别于给药后10 min、0.5、1、2、4、8、12 h后脱颈椎处死,立即解剖采集心、肝、脾、肺、肾、胃、大肠、小肠、脑等组织。各组织处理后测定其中穗花杉双黄酮的分布情况。结果:各组织在不同范围内线性关系良好,最低检测限0.125 ng,日内日间精密度均小于10%,各组织中穗花杉双黄酮的绝对回收率在75.07%-89.80%之间;相对回收率在92.00%-107.00%之间;各组织中穗花杉双黄酮在-20℃冰箱内保存15天条件下稳定性良好。结论:穗花杉双黄酮在各组织中浓度差异较大,大鼠灌服穗花杉双黄酮主要分布于胃、大肠、小肠、肝、肾中,其次为心、肺、脾中,并可透过血脑屏障分布于脑组织中。     

Increased expression of urokinase-type plasminogen activator in colorectal carcinoma and in adenomatous polyps

Human plasminogen activators (HPA) comprise the tissue type produced mainly by endothelial cells of 66 000 molecular weight (MW) which is principally involved in fibrinolysis (HPA66) and the urokinase type of 52 000 MW (HPA52) which is implicated in the invasion process of malignancy. The purpose of this study was to elucidate the pattern of HPA expression in histologically normal colonic mucosa, sporadic polyps, polyposis coli polyps, and in colon cancer tissue, to determine whether the expression of HPA52 is a correlate of neoplastic transformation of colonic epithelial cells. Homogenates of colonoscopic biopsies and resected colon tissue were subjected to polyacrylamide gel electrophoresis and the HPA activity was detected by a fibrin overlay gel. In histologically normal mucosal biopsies from non-cancer-bearing colons and in uninvolved mucosa from cancer-bearing colons, only HPA66 was detected. By contrast, all 19 colon cancer specimens expressed HPA52 and 16 of these also showed HPA66 activity. Two of three colon cancer cell lines showed HPA52 activity, but none expressed HPA66. HPA52 activity was observed in 17 of 20 adenomatous polyps, all of which displayed HPA66 activity. No correlation was found between polyp size, degree of epithelial dysplasia or the type of polyp architecture, and the semiquantitative estimates of HPA52 activity as judged by the areas of fibrinolysis generated.
This study of HPA52 in the colon epithelial neoplasms comprising adenomatous polyps, colon cancer tissue and colon cancer cell lines suggests that the transformation of the colon epithelial cell correlates with increased expression of HPA52, an enzyme that has been implicated in the invasive process of malignancy.     

Comparing computer-generated and pathologist-generated tumour segmentations for immunohistochemical scoring of breast tissue microarrays

Background:

Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review.

Methods:

In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software.

Results:

Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (κ=0.81) than between pathologists'' masks (κ=0.91), this had little impact on computed IHC scores (Allred; =0.91, Quickscore; =0.92).

Conclusions:

The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials.     

The role and therapeutic implications of RING‐finger E3 ubiquitin ligases in hepatocellular carcinoma

Increasing evidence indicates that deregulation of RING‐finger ubiquitin‐protein ligases (E3s) involves in the development of hepatocellular carcinoma (HCC). These RING‐finger E3s serve as oncoproteins or tumor suppressors in HCC under specific conditions. In this review, we summarize current knowledge about abnormal RING‐finger E3s and their clinical significance in the development of HCC, and discuss parts of critical substrates for these RING‐finger E3s in detail. Furthermore, in light of success of Bortezomib in treating hematological malignancies, we describe the preclinical and clinical studies of therapeutic approaches targeting aberrant RING‐finger E3s in HCC.