Oral Administration of Ginger-Derived Lipid Nanoparticles and Dmt1 siRNA Potentiates the Effect of Dietary Iron Restriction and Mitigates Pre-Existing Iron Overload in Hamp KO Mice

Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. High Fpn1-mediated iron export depletes intracellular iron, causing a paradoxical increase in Dmt1-mediated iron import. Increased activity of both transporters causes excessive iron absorption, thus initiating body iron loading. Logically then, silencing of intestinal Dmt1 or Fpn1 could be an effective therapeutic intervention in HH. It was previously established that Dmt1 knock down prevented iron-loading in weanling Hamp (encoding hepcidin) KO mice (modeling type 2B HH). Here, we tested the hypothesis that Dmt1 silencing combined with dietary iron restriction (which may be recommended for HH patients) will mitigate iron loading once already established. Accordingly, adult Hamp KO mice were switched to a low-iron (LFe) diet and (non-toxic) folic acid-coupled, ginger nanoparticle-derived lipid vectors (FA-GDLVs) were used to deliver negative-control (NC) or Dmt1 siRNA by oral, intragastric gavage daily for 21 days. The LFe diet reduced body iron burden, and experimental interventions potentiated iron losses. For example, Dmt1 siRNA treatment suppressed duodenal Dmt1 mRNA expression (by ~50%) and reduced serum and liver non-heme iron levels (by ~60% and >85%, respectively). Interestingly, some iron-related parameters were repressed similarly by FA-GDLVs carrying either siRNA, including ⁵⁹Fe (as FeCl₃) absorption (~20% lower), pancreatic non-heme iron (reduced by ~65%), and serum ferritin (decreased 40–50%). Ginger may thus contain bioactive lipids that also influence iron homeostasis. In conclusion, the combinatorial approach of FA-GDLV and Dmt1 siRNA treatment, with dietary iron restriction, mitigated pre-existing iron overload in a murine model of HH.     

测定白血病脑脊液中SIL—2R，IL—6表达的临床意义

为了探讨急性淋巴细胞性白血病 (ALL)患者脑脊液中可溶性白介素 - 2受体 (SIL - 2R)、白介素 6(IL - 6)的表达及意义 ,采用双抗夹心ELISA法测定 3 0例ALL患者脑脊液 (CSF)中SIL - 2R ,IL - 6水平 ,并与 10名正常者进行对照 .结果 :ALL合并中枢神经系统白血病 (CNS -L)组较CNS -L已缓解及未合并CNS -L组二者水平显著升高 (P <0 0 1) ;CNS -L已缓解组二者水平接近对照组 (P >0 0 5 ) ;骨髓缓解及好转组二者水平低于治疗无效组 .结果表明 :监测二者水平变化有助于CNS -L早期诊断、估计预后、判断疗效 .     

白细胞介素1刺激破骨细胞性骨吸收作用的实验研究

目的：了解白细胞介素1β（IL－1β）在破骨细胞性骨吸收中的刺激作用及其相应的作用机制。方法：分别将新生大鼠破骨细胞单独以及和成骨细胞联合接种于预置象牙片的培养板中。24h后培养液中加入不同浓度的IL－1β。继续培养48h,然后取出象牙片,超声处理后行甲苯胺蓝染色,光镜下观察骨吸收陷窝的数目并计算其部面积。结果：IL－1β能够明显增加坡骨细胞和成骨细胞联合培养组象牙片上吸收陷窝的数目和面前,且刺激作用呈剂量依赖性,但对单独培养的破骨细胞无明显刺激作用。结论：IL－1β的刺激骨吸收作用由成骨细胞所介导,而非直接作用于破骨细胞。     

蒿甲醚合成母液中一个新成分的分离和鉴定

目的：为了弄清蒿甲醚合成母液中的衍生杂质结构及开发新的药源。方法：用色谱法从合成蒿甲醚的母液中分离其衍生物成分,并用化学波谱法鉴定其结构,结果：分离得到5个化合物分别鉴定为α-蒿甲醚（Ⅰ）,二氢青蒿素（Ⅱ）,青蒿素（Ⅲ）,八氢－8－甲氧基－4,7－二甲基－呋喃[3,2-i]苯并吡喃－10－乙酸酯（Ⅳ）和12－脱氧－11－烯青蒿素（Ⅴ）。结论：化合物Ⅴ为一新化合物,命名为12－脱氧－11－烯青蒿素,并首次从合成蒿甲醚的母液中得到。     

胆道结石术后继发急性胆管炎病原菌及sCD14-ST和IL-8的诊断价值

目的探讨胆道结石术后继发急性胆管炎病原菌及可溶性CD14亚型(sCD14-ST)、白细胞介素-8(IL-8)的诊断价值。方法选择海南医学院第一附属医院2017年1月-2019年6月收治的胆道结石术后继发急性胆管炎患者62例作为研究对象,纳入研究组,选择同期医院收治的胆道结石术后未继发急性胆管炎的患者60例设为对照组;对研究组患者病原菌进行统计;比较不同急性胆管炎程度、不同预后结局患者血清sCD14-ST、IL-8水平;采用受试者工作特征曲线评估血清sCD14-ST、IL-8水平对于患者不良预后的诊断价值。结果 62例患者共培养分离病原菌67株,其中革兰阴性菌43株占64.18%,革兰阳性菌21株占31.34%,真菌3株占4.48%,以大肠埃希菌为主;重度急性胆管炎患者血清sCD14-ST、IL-8分别为(91.38±25.67)pg/ml、(45.28±13.61)pg/ml高于中度患者分别为(74.34±19.65)pg/ml、(32.06±10.44)pg/ml及轻度患者(P均<0.001),中度患者血清sCD14-ST、IL-8水平高于轻度患者(P均<0.001);预后不良患者急性胆管炎血清sCD14-ST、IL-8分别为(89.84±25.09)pg/ml、(41.94±12.28)pg/ml高于预后良好患者(P<0.05);sCD14-ST、IL-8对胆道结石术后急性胆管炎患者预后的截断值分别为65.65、29.31 pg/ml,其曲线下面积分别为0.841、0.768。结论胆道结石术后继发急性胆管炎病原以革兰阴性菌为主;运用血清sCD14-ST、IL-8可较好区分疾病严重程度,且对患者预后具有一定预测价值。     

人参总皂甙对造血生长因子产生的影响

本文应用造血祖细胞体外培养术和白细胞介素（ＩＬ）生物活性检测术，观察经人参总皂甙（ＴＳＰＧ）刺激的小鼠脾细胞、腹腔巨噬细胞和成纤维细胞培养上清液的集落刺激因子（ＣＳＦ）、ＩＬ－２和ＩＬ－６生物活性。结果表明：ＴＳＰＧ刺激组的ＣＳＦ和ＩＬ－６活性均显著高于对照组，ＴＳＰＧ刺激的脾细胞培养上清液的ＩＬ－２活性明显高于对照组，而ＴＳＰＧ刺激的巨噬细胞和成纤维细胞培养上清液的ＩＬ－２活性与对照组无显著性差     

No justification of routine screening for 22q11 deletions in patients with overt cleft palate

The velo-cardio-facial syndrome (VCFS), caused by a submicroscopic deletion of chromosome 22q11, is the most common syndrome that has palatal anomalies as a major feature. A possible strategy for early detection of VCFS is routine screening for 22q11 deletions in all infants with cleft palate (CP). The purpose of this study was to evaluate whether this strategy is preferable to testing on clinical suspicion. At the Nijmegen Cleft Palate Craniofacial Center, 58 new patients with overt CP were routinely tested, using fluorescence in situ hybridization (FISH), for a 22q11 deletion. One deletion was identified in a newborn girl with an overt CP who was clinically not suspected of having VCFS. Based on this study (n = 45) and the literature (n = 54), the prevalence of 22q11 deletions among children with CP, but without any other symptoms of VCFS, is estimated to be one in 99. We take the view that this figure is rather low and that early discovery will rarely have significant clinical or genetic consequences. Because CP patients remain under medical attention, almost all of the infants with isolated CP and VCFS will be recognized as having the syndrome at a later age when additional features have developed. Therefore, we conclude that routine FISH testing for 22q11 deletions in infants with overt CP is not indicated, provided clinical follow-up is guaranteed.     

Interleukin-6 and selected plasma proteins in healthy persons of different ages

In the present study, interleukin-6(IL-6) and several acute phase proteins were measured in healthy participants (23–87 years of age). A linear correlation between IL-6 and age was established with an increase of 0.016 pg/ml(00.004) per year of life. Whereas CRP remained below 0.5 mg/dl in all participants, an increase with age for fibrinogen and an inverse relation for albumin as well as transferrin were obtained. However, the increase of IL-6 did not correlate with any of these changes. IL-6 associated diseases may therefore occur more often with advancing age, but in healthy participants IL-6 does not explain the changing plasma protein pattern resembling that of an acute phase reaction.