Expression of Putative Stem Cell Marker,Hepatocyte Nuclear Factor 4 Alpha,in Mammary Gland of Water Buffalo

Buffaloes account for more than 56% of total milk production in India. Cyclic remodeling of mammary glands of human, mice, cow, sheep, and goat is determined by mammary stem cells. It is logical to assume that buffalo mammary gland will have mammary stem/progenitor cells. Thus far, no report exists on identification of buffalo mammary stem cells. Hepatocyte nuclear factor 4 alpha (HNF4A) is a candidate marker for hepatic progenitor cells and has recently been suggested as a marker of bovine mammary stem/progenitor cells. We hypothesized that (1 Pasha TN, Hayat Z. Present situation and future perspective of buffalo production in Asia. J Anim Plant Sci 2012; 22(3 supple.):250–256. [Google Scholar]) HNF4A identifies putative buffalo mammary stem/progenitor cells and (2 NDDB. National Dairy Development Board. 2015. http://www.nddb.org/English/Statistics/Pages/Milk-Production.aspx. Accessed May 10, 2015. [Google Scholar]) the number of HNF4A-positive cells increases during mastitis. Sixteen buffalo mammary samples were collected from a local slaughterhouse. Hematoxylin and eosin staining were performed on 5-micron thick sections and on the basis of gross examination and histomorphology of the mammary glands, physiological stages of the animals were estimated as non-lactating (n = 4), mastitis (n = 9), and prepubertal (n = 3). In total, 24048 cells were counted (5–10 microscopic fields/animal; n = 16 animals) of which, 40% cells were mammary epithelial cells (MEC) and 60% cells were the stromal cells. The percentage of MEC in non-lactating animals was higher compared to mastitic animals (47.3% vs. 37.3%), which was likely due to loss of MEC in mastitis. HNF4A staining was observed in nuclei of MEC of ducts, alveoli, and stromal cells. Basal location and low frequency of HNF4A-positive MEC (ranges from 0.4–4.5%) were consistent with stem cell characteristics. Preliminary study showed coexpression of HNF4A with MSI1 (a mammary stem cell marker in sheep), suggesting HNF4A was likely to be a putative mammary stem/progenitor cell marker in buffalo. HNF4A-positive MEC (basal and luminal; light and dark stained) tended to be higher in non-lactating than the mastitic animals (8.73 ± 1.71% vs. 4.29 ± 1.19%; P = 0.07). The first hypothesis that HNF4A identify putative mammary stem/progenitor cells was confirmed but the second hypothesis that the number of mammary stem/progenitor cells decreases during mastitis was unsupported. This is the first report outlining the expression of HNF4A and identification of putative mammary stem/progenitor cells in buffalo mammary gland.     

Fetuin A is down-regulated in rats during heterotopic ossification after Achilles tenotomy

We investigated the role of fetuin A during heterotopic ossification (HO) in rats following Achilles tenotomy. We performed a right midpoint Achilles tenotomy on 24 rats. At 5 and 10 h after surgery, we investigated the formation of ectopic bone using X-ray and histological examination. We evaluated the mRNA level of fetuin A using real-time PCR. Presence of fetuin A in the Achilles tendon was assessed by immunohistochemical staining. We also measured the serum concentration of fetuin A using enzyme linked immunosorbent assay (ELISA). The expression of fetuin A was significantly decreased in both the liver and Achilles tendon during HO. ELISA showed a small amount of fetuin A in blood throughout the development of HO. Immunohistochemical staining showed that fetuin A was abundant in the ectopic bone. Fetuin A appears to be involved in the formation of ectopic bone induced by Achilles tenotomy, and a deficiency of fetuin A plays a role in the development of HO.     

非ST段抬高型急性冠脉综合征患者血浆S100A1水平与GRACE评分及短期预后相关性的研究

目的:探讨非ST段抬高型急性冠脉综合征(NST-ACS)患者血浆S100A1水平与全球急性冠状动脉事件注册(GRACE)评分之间的关系,以及S100A1水平对NST-ACS患者30天预后的判定价值。方法:共有162例NST-ACS患者符合入选标准,收集基本临床资料,进行GRACE评分,同时收集次日清晨空腹采集肘静脉血,检测血浆S100A1浓度,与患者的GRACE评分进行比较。根据S100A1的水平进行分组随访,KM生存分析不同组患者30天预后进行评价。结果:不同GRACE分组患者间S100A1水平具有显著性差异(P0.05);相关性分析显示,NST-ACS患者S100A1与GRACE评分呈显著正相关(r=0.49,P0.01);KM生存分析显示,S100A1水平3.41 ng/mL的患者30天内心血管事件发生率显著升高(P0.05)。结论:S100A1可作为预测NST-ACE患者病情的发生发展的生化指标;在NST-ACS患者中运用S100A1有助于对患者早期危险分层及评估预后有一定的临床价值。     

呼吸窘迫综合征早产儿血清VA、PCT、TNF-α及CRP水平的表达及临床意义

目的:探讨呼吸窘迫综合征(RDS)早产儿血清维生素A(VA)、降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)及C反应蛋白(CRP)水平的表达及临床意义。方法:选取2015年2月～2018年5月期间青岛市妇女儿童医院收治的90例RDS早产儿纳入观察组,根据RDS分级将观察组分为轻度组48例,中重度组42例。另选取同期于本院出生的非RDS早产儿35例作为对照组。根据血清VA水平将125例早产儿分为VA缺乏组(n=72),亚临床VA缺乏组(n=36),正常组(n=17)。比较观察组与对照组、轻度组与中重度组早产儿血清VA、PCT、TNF-α及CRP水平,比较不同血清VA水平早产儿的RDS发病情况,分析观察组早产儿血清VA与PCT、TNF-α及CRP水平的相关性。结果:观察组早产儿血清VA水平明显低于对照组(P0.05),而观察组早产儿血清PCT、TNF-α、CRP明显高于对照组(P0.05)。中重度组早产儿血清VA水平与轻度组比较差异无统计学意义(P0.05),而中重度组早产儿血清PCT、TNF-α、CRP水平明显高于轻度组(P0.05)。随着血清VA水平的升高,RDS发病率逐渐降低,组间比较差异有统计学意义(P0.05)。Pearson相关性分析显示,观察组早产儿血清VA与PCT、TNF-α及CRP水平无显著相关性(P0.05)。结论:RDS早产儿血清VA与PCT、TNF-α及CRP水平均存在明显异常,但四者无明显相关性,血清VA相对较低者更易发生RDS,临床可通过及时干预VA水平以降低RDS的发生风险。     

老年冠心病患者血清Lp-PLA2、hs-CRP、IL-27及MMP-9水平与Gensini积分的相关性研究*

目的:探讨老年冠心病患者血清脂蛋白相关磷脂酶A2(Lp-PLA2)、高敏C反应蛋白(hs-CRP)、白细胞介素-27(IL-27)及基质金属蛋白酶-9(MMP-9)水平与Gensini积分的相关性。方法:选取2015年10月至2018年2月我院收治的冠心病患者142例为研究对象,将所有患者按照不同的冠心病类型分为不稳定型心绞痛(UAP)组54例、稳定型心绞痛(SAP)组40例和急性心肌梗死(AMI)组48例。同时根据患者Gensini积分将其分为轻度47例、中度51例和重度44例。比较不同冠心病类型、不同严重程度的Lp-PLA2、hs-CRP、IL-27、MMP-9水平及Gensini积分,并分析冠心病患者上述指标水平与Gensini积分的相关性。结果:AMI组患者Lp-PLA2、hs-CRP、IL-27、MMP-9水平及Gensini积分均高于UAP组和SAP组,且UAP组高于SAP组(P0.05)。重度患者Lp-PLA2、hs-CRP、IL-27、MMP-9水平及Gensini积分均高于中度和轻度患者,且中度患者高于轻度患者(P0.05)。经Spearman相关性分析结果显示,冠心病患者Lp-PLA2、hs-CRP、IL-27、MMP-9水平与Gensini积分均呈正相关(P0.05)。结论:老年冠心病患者Lp-PLA2、hs-CRP、IL-27及MMP-9水平与患者冠状动脉病变Gensini积分均呈正相关。临床根据Lp-PLA2、hs-CRP、IL-27及MMP-9水平的变化,有助于评估老年冠心病患者的病情严重程度。     

高通量血液透析治疗慢性肾衰竭尿毒症的疗效及对尿毒症毒素、免疫球蛋白及肺功能指标的影响

目的:探讨高通量血液透析(HFHD)治疗慢性肾衰竭尿毒症的疗效及对尿毒症毒素、免疫球蛋白及肺功能指标的影响。方法:选取90例于2012年1月-2017年3月期间在喀什地区第一人民医院治疗的慢性肾衰竭尿毒症患者,依据随机数字表法将其分为对照组(n=45)和观察组(n=45),对照组给予血液透析滤过(HDF)治疗,观察组给予HFHD治疗,两组均透析治疗1个月。对比两组患者透析前后症状缓解情况及尿毒症毒素、免疫球蛋白及肺功能指标水平,记录两组相关并发症的发生情况。结果:透析治疗结束后观察组患者缓解率为91.11%(41/45),高于对照组的73.33%(33/45)(P0.05)。两组患者透析后血磷(P~-)、血钾(K~+)、甲状旁腺激素(PTH)、β2-微球蛋白(β2-MG)水平明显低于透析前,血钙(Ca~(2+))水平明显高于透析前(P0.05);观察组透析后K~+、Ca~(2+)、P~-等尿毒症毒素水平与对照组比较差异无统计学意义(P0.05),观察组透析后PTH、β2-MG水平明显低于对照组(P0.05)。透析后,两组患者的免疫球蛋白Ig M、Ig A、Ig G水平均较透析前上升,且观察组高于对照组(P0.05)。透析后,两组患者残气量(RV)均低于治疗前,最大肺活量(FVC)、肺活量(VC)、肺总量(TLC)均高于治疗前,且观察组RV低于对照组,FVC、VC、TLC均高于对照组(P0.05)。观察组并发症发生率为8.89%(4/45),低于对照组的24.44%(11/45)(P0.05)。结论:HFHD治疗慢性肾衰竭尿毒症能够安全有效地清除尿毒症毒素,缓解患者的临床症状,且能够提高患者的免疫功能和肺功能。     

乙醛脱氢酶2可减少氧化损伤诱导的心肌细胞凋亡

乙醛脱氢酶2 (aldehyde dehydrogenase 2, ALDH2)是线粒体特异性酶,已被证明参与氧化应激诱导的细胞凋亡,而在心肌细胞中的作用知之甚少。本研究旨在通过用特异性ALDH2抑制剂大豆苷抑制ALDH2活性来研究ALDH2在抗霉素A诱导的心肌细胞凋亡中的作用。应用抗霉素A和大豆苷诱导小鼠心肌细胞,然后测定ALDH2酶活性、细胞内活性氧(reactive oxy gen species, ROS)含量和细胞凋亡,应用RT-PCR和蛋白质印迹法(Western blotting)检测ALDH2 m RNA和蛋白表达。结果表明,抗霉素A (40μg/mL)可诱导新生心肌细胞凋亡,而大豆苷(50μmol/L)能有效地抑制ALDH2活性而对细胞凋亡没有影响,并且可显著增强抗霉素A诱导的心肌细胞凋亡(53.72%～71.33%, p<0.05)。与单独用抗霉素A处理的细胞相比,抗霉素A和大豆苷共处理的心肌细胞中活化的丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)信号传导途径(p38-MAPK)的磷酸化也显著增加。本研究初步表明,改变线粒体ALDH2活性可能是减少氧化损伤诱导的心肌细胞凋亡的潜在选择。     

MiR‐802 causes nephropathy by suppressing NF‐κB‐repressing factor in obese mice and human

Obesity is associated with significant microvascular complications including renal injuries and may induce end‐stage renal disease. Emerging studies have demonstrated microRNAs (miRNAs) are potential mediators in the pathophysiological process of nephropathy. The present study aimed to investigate the role of miR‐802 in obesity‐related nephropathy and potential molecular mechanisms. Through utilizing obese mouse model and human subjects, we explored the therapeutic benefits and clinical application of miR‐802 in protecting against nephropathy. Renal miR‐802 level was positively correlated with functional parameters, including blood urea nitrogen and creatinine in obese mice. Specific silencing of renal miR‐802 improved high fat diet (HFD)‐induced renal dysfunction, structural disorders and fibrosis. The up‐regulated inflammatory response and infiltrated macrophages were also significantly decreased in miR‐802 inhibitor‐treated obese mice. Mechanistically, miR‐802 directly bond to 3?‐UTR of NF‐κB‐repressing factor (NRF) and suppressed its expression. In clinical study, the circulating miR‐802 level was significantly increased in obese subjects, and positively correlated with plasma creatinine level but negatively correlated with creatinine clearance. Taken together, our findings provided evidence that miR‐802/NRF signalling was an important pathway in mediating obesity‐related nephropathy. It is a possible useful clinical approach of treating miR‐802 inhibitor to combat nephropathy.