Enhanced tumour growth in the rat liver after selective elimination of Kupffer cells

The evidence that Kupffer cells are capable of controlling metastatic growth in the liver in vivo is largely circumstantial. The best approach when studying natural cytotoxicity activities of Kupffer cells is to investigate the effect of Kupffer cell elimination on tumour growth. Until now it has not been possible to eliminate Kupffer cells without affecting other cell populations. We have recently developed a new method to eliminate Kupffer cells selectively: intravenous injection of liposome-encapsulated (dichloromethylene)bisphosphonate (Cl₂MDP-liposomes) leads to effective elimination of all Kypffer cells, without affecting non-phagocytic cells. Wag/Rij rats were injected with Cl₂MDP-liposomes. After 48 h, rats were inoculated with syngeneic CC531 colon carcinoma cells by injection in the portal system. The results show a strongly enhanced tumour growth in the liver of the Cl₂MDP-liposometreated rats. In these animals, livers were almost completely replaced by tumour and had increased in weight, whereas in the control groups only a few (four to eight) small (1-mm) tumour nodules were found. These data show that selective elimination of Kupffer cells results in enhanced tumour growth in the liver, implying that Kupffer cells play a crucial role in controlling tumour growth in the liver.     

Rare earth cerium oxide nanoparticles attenuated liver fibrosis in bile duct ligation mice model

Liver fibrosis is one of the major liver complications which eventually progresses to liver cirrhosis and liver failure. Cerium oxide nanoparticles, also known as nanoceria (NC) are nanoparticles with potential antioxidant and anti-inflammatory activities. Herein, we evaluated the hepatoprotective and anti-fibrotic effects of nanoceria (NC) against bile duct ligation (BDL) induced liver injury. NC were administered i.p. for 12 days (0.5 and 2 mg/kg) to C57BL/6J mice. The biochemical markers of liver injury, oxidative and nitrosative stress markers, inflammatory cytokines were evaluated. Fibrosis assessment and mechanistic studies were conducted to assess the hepatoprotective effects of NC. Administration of NC proved to significantly ameliorate liver injury as evident by reduction in SGOT, SGPT, ALP and bilirubin levels in the treated animals. NC treatment significantly reduced the hydroxyproline levels and expression of fibrotic markers. In summary, our findings establish the hepatoprotective and anti-fibrotic effects of NC against BDL induced liver injury and liver fibrosis. These protective effects were majorly ascribed to their potential ROS inhibition and antioxidant activities through catalase, superoxide dismutase (SOD)-mimetic properties and auto-regenerating capabilities.     

Effect of thyroidectomy and adrenalectomy on changes in liver glutathione and malonaldehyde levels after acute ethanol injection

At low concentrations ethanol is metabolized largely by alcohol dehydrogenase to acetaldehyde, while at higher concentrations a microsomal ethanol oxidising system (MEOS) is involved, namely cytochrome P450 IIE1, which also probably generates free radical species. In hyperthyroidism hepatic glutathione stores are depleted and net superoxide anion production occurs. In contrast, in hypothyroidism hepatic glutathione may be increased and thus renders the liver less sensitive to alcohol generated free radical production. Steroid hormones inhibit lipid peroxidation. Sixty male Wistar rats either underwent thyroidectomy, adrenalectomy, or sham procedures. Twenty control animals were pair fed with thyroidectomized animals, whilst another twenty fed ad libitum. An intraperitoneal injection of alcohol (75 mmol/kg) was given 2.5 h prior to sacrifice to half the animals in each group, the remainder receiving saline. The total hepatic glutathione contents of the pair fed and the ad libitum groups were not different, but were significantly increased by thyroidectomy (p = <0.001). This effect was significantly reduced by alcohol (p < 0.01). The sham procedures and dietary restrictions had no effect. The ethanol alone reduced total hepatic glutathione, but this only reached statistical significance in the thyroidectomized and sham-adrenalectomized groups. Hepatic malonaldehyde (MDA) levels were significantly reduced in the thyroidectomy group but alcohol had no effect on them. We conclude that hypothyroidism increased hepatic glutathione status, presumably by reducing radical production by enzyme systems, which would otherwise consume this important scavenger. Long term exposure to ethanol with induction of MEOS is probably required for it to generate toxic levels of free radical species.     

A carbon-13 nuclear magnetic resonance investigation of the metabolic fluxes associated withy glucose metabolism in human erythrocytes

We have used [2-¹³C]d-glucose and carbon-13 nuclear magnetic resonance (NMR) spectroscopy to investigate metabolic fluxes through the major pathways of glucose metabolism in intact human erythrocytes and to determine the interactions among these pathways under conditions that perturb metabolism. Using the method described, we have been able to measure fluxes through the pentose phosphate pathway, phosphofructokinase, the 2,3-diphosphoglycerate bypass, and phosphoglycerate kinase, as well as glucose uptake, concurrently and in a single experiment. We have measured these fluxes in normal human erythrocytes under the following conditions: (1) fully oxygenated; (2) treated with methylene blue; and (3) deoxygenated. This method makes it possible to monitor various metabolic effects of stresses in normal and pathological states. Not only has ¹³C-NMR spectroscopy proved to be a useful method for measuring in vivo flux through the pentose phosphate pathway, but it has also provided additional information about the cycling of metabolites through the non-oxidative portion of the pentose phosphate pathway. Our evidence from experiments with [1-¹³C]-, [2-¹³C]-, and [3-¹³C]d-glucoses indicates that there is an observable reverse flux of fructose 6-phosphate through the reactions catalyzed by transketolase and transaldolase, even in the presence of a net flux through the pentose phosphate pathway.     

Preparation and Characterization of a Silk Fibroin/Polyurethane Fiber Blend Membrane Containing Actinomycin X2 with Excellent Mechanical Properties and Enhanced Antibacterial Activities

Development of suitable antimicrobial biomaterials for hygienic wound dressing and healing is an important requirement for medical application. Durable mechanical properties increase the application range of biomaterial in different environmental and biological conditions. Due to the inherent brittleness of silk fibroin (SF), polyurethane fiber (PUF) was used to modify SF containing actinomycin X2 (Ac.X2) to prepare silk fibroin@actinomycin X₂/polyurethane fiber (ASF/PUF) blend membranes. The ASF/PUF blend membrane was developed by solution casting method. Incorporation of PUF improved the flexibility of material and introduction of Ac.X2 has increased antibacterial activity of materials. Excellent mechanical properties (tensile strength up to 25.7 MPa and elongation at break up to 946.5 %) of 50 % SF+50 % PUF blend membrane were proved by tensile testing machine. FT-IR spectra, TGA, contact angle and DMA were tested to prove the blend membrane's physico-chemical characteristics. ASF/PUF blend membrane displayed satisfactory antibacterial activity against S. aureus, and the cytotoxicity tests showed that the blend membrane has better biosafety compared to directly applied Ac.X2 in soluble form. These results suggest that the modification of SF through PUF for development of flexible antibacterial membranes has great potential application value in the field of silk-like material fabrication.     

传染性单核细胞增多症患儿NLR、CD4+/CD8+比值、ADA与EBV-DNA载量的相关性分析及对肝损害的影响

摘要 目的：探讨传染性单核细胞增多症（IM）患儿外周血中性粒细胞/淋巴细胞比值（NLR）、CD4⁺/CD8⁺比值、腺苷脱氨酶（ADA）与EB病毒（EBV）-脱氧核糖核酸（DNA）载量的相关性,分析其对IM患儿肝损害的影响。方法：选择2019年1月至2022年4月我院儿科收治的102例IM患儿（IM组）,另选择同期我科收治的95例EB病毒检测阴性的发热患儿（非IM组）和体检健康的73例健康儿童（对照组）。根据是否发生肝损害将IM患儿分为肝损害组（61例）和非肝损害组（41例）。比较外周血NLR、CD4⁺/CD8⁺比值、ADA与EBV-DNA载量,Pearson法分析NLR、CD4⁺/CD8⁺比值、ADA与EBV-DNA载量的相关性。多因素Logistic回归分析IM患儿发生肝损害的影响因素。结果：IM组ADA高于非IM组和对照组（P＜0.05）,且非IM组高于对照组（P＜0.05）,NLR、CD4⁺/CD8⁺比值低于非IM组和对照组（P＜0.05）,且非IM组低于对照组（P＜0.05）,IM组EBV-DNA载量高于非IM组（P＜0.05）。IM患儿ADA与EBV-DNA载量呈正相关（r=0.493,P＜0.05）,NLR、CD4⁺/CD8⁺比值与EBV-DNA载量呈负相关（r=-0.419、-472,P＜0.05）。肝损害组ADA、EBV-DNA载量高于非肝损害组（P＜0.05）,NLR、CD4⁺/CD8+⁺比值低于非肝损害组（P＜0.05）。肝脏肿大、高EBV-DNA载量、高ADA是IM患儿肝损害的危险因素（P＜0.05）,高NLR、高CD4⁺/ CD8⁺比值是保护因素（P＜0.05）。结论：IM患儿ADA增高,NLR、CD4⁺/CD8⁺比值降低,与EBV-DNA载量增加以及肝损害有关。     

探究壮方柔肝化纤颗粒对肝纤维化大鼠肝组织病理影响机制

摘要 目的：探究壮方柔肝化纤颗粒对肝纤维化大鼠肝组织病理影响机制。方法：选取80只雄性Wistar大鼠随机将其平均分成正常对照组、病理模型组、柔肝化纤颗粒低、中、高剂量组,每组各16只。四氯化碳复合因素造模,观察记录大鼠肝脏形态,采用HE染色、Masson染色观察大鼠肝组织和胶原纤维变化,检测血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）指标数值,分析大鼠肝组织中谷胱甘肽过氧化物酶（GSH-Px）、羟脯氨酸（HYP）、超氧化物歧化酶（SOD）与丙二醛（MDA）的含量。结果：柔肝化纤颗粒低、中、高剂量组大鼠肝细胞变性、坏死及纤维化组织增生程度均较病理模型组明显减轻。柔肝化纤颗粒低、中、高剂量组血清ALT、AST指标数值与肝组织中HYP、MDA指标水平较病理模型组呈现剂量依赖性降低（P＜0.001）,而柔肝化纤颗粒高剂量组GSH-Px、SOD的指标含量显著高于病理模型组,差异均有统计学意义（P＜0.001）。结论：柔肝化纤颗粒可有效改善肝纤维化大鼠的肝细胞损害情况,减轻其肝组织炎症程度,对肝纤维化大鼠有一定的保肝护肝与抗肝纤维化作用,其机制可能与提高GSH-Px与SOD的水平、降低HYP与MDA的含量、降低氧化应激水平、调节脂质代谢、减少机体胶原蛋白合成等相关。     

原位缺口平移标记断裂DNA技术及其在检测流行性出血热尸检和实验动物组织中细胞凋亡和早期死亡的应用

原位缺口平移技术（ＩＳＮＴ）已被用于检测细胞核中ＤＮＡ断裂鉴别尸检组织中细胞的凋亡和坏死断裂、流行性出血热（ＥＨＦ）组织中存在散在单个细胞变性死亡和灶性梗死样坏死,前者带有细胞凋亡的特征。本文以ＥＨＦ肝脏和实验性病毒感染鼠脑组织为例,应用缺口平移法,在ＤＮＡ聚合酶或Ｋｌｅｎｏｗ酶的作用下,将地高辛标记的ｄＵＴＰ掺入合成到ＤＮＡ的断裂部位,通过碱性磷酸酶标抗地高辛抗体免疫组化法显示细胞ＤＮＡ的断裂,检测和鉴别细胞的凋亡和坏死。为分析死后解剖时间间隔及组织固定时间对该方法的影响,本文选用死后２～１４０ｈ尸检、经常规固定石蜡包埋后存放１０～３５年的标本和在１０％福尔马林固定了１０～３５年之后再进行常规处理的标本。实验时用蛋白酶Ｋ（ＰＫ）消化前后对比并分别在标记反应液中略去ＤＮＡ聚合酶作为阴性对照,用ＤＮＡ酶消化组织人为制造ＤＮＡ缺日作为阳性对照。结果发现,未经ＰＫ消化的组织,仅灶性肝细胞核ＩＳＮＴ标记阳性,经ＰＫ消化后,散在的带有凋亡特征的肝细胞胞核也出现阳性,灶性肝细胞胞核标记染色增强,但无论是蛋白酶消化与否,明确梗死样坏死的肝细胞均不被标记。结果还发现,死后２～２４ｈ内尸检组织和长时间（１０～３４年）存放的石     

肝炎平对D－氨基半乳精所致肝损害保护作用的酶组织化学研究

本实验采用Ｄ－氨基半乳糖（Ｄ－ＧａｌＮ）诱导的大鼠急性肝损伤模型,观察大鼠肝脏组织化学的变化,探讨肝炎平对急性肝损伤的保护作用。实验分为四组,即正常对照组、模型组、肝炎平及肝得健保护组。结果表明：肝炎平对肝细胞膜系统有一定的保护作用。肝炎平组和肝得健组ＳＤＨ、ＣＣＯ及ＣｈＥ活性明显高于模型组,且与正常对照组相近。本实验模型组ＡＣＰ的活性明显高于正常组,而肝炎平组ＡＣＰ的活性明显低于模型组,与正常对照组无显著性差异。提示：肝炎平可显著改善因Ｄ－氨基半乳糖所致肝损害的作用。且其对肝细胞的保护作用与肝得健一致。     

Morphometric Analysis of Hepatocellular carcinoma

Ｍｏｒｐｈｏｍｅｔｒｉｃ　Ａｎａｌｙｓｉｓ　ｏｆ　Ｈｅｐａｔｏｃｅｌｌｕｌａｒ　ｃａｒｃｉｎｏｍａＬａｉＭａｏ－ｄｅ（来茂德）;ＣｈｅｎＰｅｉ－ｈｕｉ（陈培辉）ａｎｄＺｈｏｕＳｈｕｉ－ｙｕｎ（周水云）（ＤｅｐａｒｔｍｅｎｔｏｆＰａｔｈｏｌｏｇｙ,Ｚｈ...