洋地黄毒苷对裸鼠甲状腺乳头状癌组织生长的抑制作用

目的:探讨洋地黄毒苷对裸鼠甲状腺乳头状癌的治疗效果。方法:建立裸鼠肿瘤模型后，分为空白对照组、实验组，每组8只，分别给予生理盐水、洋地黄毒苷（1 mg/kg），隔日腹腔注射。治疗15天后，分析肿瘤体积，取下瘤体，选取实验组及空白对照组肿瘤组织进行HE染色。结果:治疗前，空白对照组与实验组裸鼠肿瘤体积分别为(109.43±7.67)mm3和(107.15±6.97)mm3。治疗15天后，空白对照组裸鼠肿瘤体积为（732.67±72.40）mm3，实验组裸鼠肿瘤体积为（251.91±27.29）mm3(实验组vs空白对照组，P<0.01）。HE染色结果示，实验组部分区域肿瘤细胞核淡染、缩小，且局部出现了变性、坏死。表明了洋地黄毒苷的抑瘤作用可能与其诱导肿瘤组织的破坏有关。结论:洋地黄毒苷可以抑制裸鼠体内甲状腺乳头状癌的生长。     

Reduction of BMP6‐induced bone formation by calcium phosphate in wild‐type compared with nude mice

Nude mice have been extensively used to investigate the potency of tissue engineering strategies for bone repair. However, the contribution of pro‐inflammatory and proregenerative stimuli of the host for the process of new bone formation and integration remains poorly understood. In this study, ectopic bone formation was investigated in nude (Nu) versus wild‐type (WT) mice. Calcium phosphate (CaP) scaffolds (CopiOs [Zimmer] and Bio‐Oss [Geistlich]) were loaded with different concentrations of rhBMP6 (40, 120, and 240 ng/mm³ rhBMP6) and implanted subcutaneously in Nu (BALB/c and NMR1) and WT (BALB/c and c57BL/6) mice. CaP scaffolds loaded with rhBMP6 did not form bone in WT mice. However, in Nu mice, 40 ng/mm³ rhBMP6 was sufficient to generate relevant volumes of new bone at 6 weeks after implantation. Looking into potential underlying mechanisms, TNF‐α blocking antibodies were injected intraperitoneally but could not restore bone formation. Also, mouse periosteal cells (mPDCs) seeded in CopiOs loaded with rhBMP6 did not significantly improve the outcome. Abrogation of bone formation was associated with dense cellular infiltration, in particular with the presence of CD3+ T‐lymphocytes. To probe a correlation between calcium ions and impaired bone formation in WT mice, type 1 collagen gels were loaded with rhBMP6 and calcium chloride and injected subcutaneously. These gels generated new bone in WT mice despite the increased percentage of CD3+ cells at Day 3 after implantation as compared with control gels. Overall, this study illustrated the negative effect of the inflammatory host response on the bone‐forming capacity of rhBMP6 coated on bioceramic scaffolds.     

JNK信号通路在小鼠术后肠麻痹发病机制中的作用

目的 探讨JNK信号通路在小鼠术后肠麻痹（POI）发病机制中的作用。方法 将野生型C57/BL6小鼠（WT）及同品系的JNK-/-小鼠均随机分成假手术组（Sham组，n=6）和肠麻痹组（POI组，n=6）。采用经典小肠操作方法诱导POI模型，术后24h给小鼠碳末灌胃，20min后麻醉小鼠，开腹取小肠评估肠动力，取回肠评估组织学改变，检测髓过氧化物酶（MPO）、IL-1β、IL-6水平及Claudin-2蛋白表达。结果 与Sham组小鼠相比，无论WT或JNK-/-小鼠其POI组的小肠排推率（分别为21%与33%）均明显降低（P=0.034及P=0.045，均P<0.05），小肠组织MPO活性水平（分别为0.608U/g与0.433U/g）明显升高（均P<0.05）；与WT小鼠POI组比较，JNK-/-小鼠POI组的小肠运动功能及其组织病理变化有所改善，炎症介质如MPO、IL-1β及IL-6水平均有明显降低（均P<0.05），小肠Claudin-2蛋白表达也降低（P<0.01）。结论 JNK基因敲除减轻小鼠肠道炎症反应、改善POI，表明JNK信号通路参与POI的发病过程。     

4-Carvomenthenol ameliorates the murine combined allergic rhinitis and asthma syndrome by inhibiting IL-13 and mucus production via p38MAPK/NF-κB signaling pathway axis

The aim of this study was to analyze the 4-carvomenthenol (carvo) oral treatment on the experimental model of the combined allergic rhinitis and asthma syndrome (CARAS). BALB/c mice were OVA-sensitized on day zero and 7th (50 μg/mL OVA in 10 mg/mL Al (OH)3) and OVA-challenged (5 mg/mL, 20 μL/animal) for three weeks. In the last week, the animals were dally challenged with aerosol of OVA and the carvo treatment (12.5, 25 or 50 mg/kg) occurred one hour before each OVA-challenge. Data were analyzed and p < 0.05 was considered significant. Carvo (12.5–50 mg/kg) decreased significantly the eosinophil migration into the nasal (NALF) and bronchoalveolar (BALF) cavities as well as on the nasal and lung tissues of sick animals. The treatment also decreased mucus production on both tissue sections stained with PAS (periodic acid-Schiff satin). In addition, the histological analyzes demonstrated that sick mice presented hyperplasia and hypertrophy of the lung smooth muscle layer followed by increasing of extracellular matrix and carvo (50 mg/kg) inhibited these asthmatic parameters. We analyzed the allergic rhinitis signals as nasal frictions and sneezing and observed that carvo decreased these two signals as well as serum OVA-specific IgE titer, type 2 cytokine synthesis, mainly IL-13, with increasing of IL-10 production. Decreasing of IL-13 production corroborated with decreasing of mucus production and these effects were dependent on p38MAPK/NF-κB(p65) signaling pathway inhibition. Therefore, these data demonstrated that a monoterpene of essential oils presents anti-allergic property on an experimental model of CARAS suggesting a new drug prototype to treat this allergic syndrome.     

Heterogeneous vestibulocerebellar mossy fiber projections revealed by single axon reconstruction in the mouse

A significant population of neurons in the vestibular nuclei projects to the cerebellum as mossy fibers (MFs) which are involved in the control and adaptation of posture, eye-head movements, and autonomic function. However, little is known about their axonal projection patterns. We studied the morphology of single axons of medial vestibular nucleus (MVN) neurons as well as those originating from primary afferents, by labeling with biotinylated dextran amine (BDA). MVN axons (n = 35) were classified into three types based on their major predominant termination patterns. The Cbm-type terminated only in the cerebellum (15 axons), whereas others terminated in the cerebellum and contralateral vestibular nuclei (cVN/Cbm-type, 13 axons), or in the cerebellum and ipsilateral vestibular nuclei (iVN/Cbm-type, 7 axons). Cbm- and cVN/Cbm-types mostly projected to the nodulus and uvula without any clear relationship with longitudinal stripes in these lobules. They were often bilateral, and sometimes sent branches to the flocculus and to other vermal lobules. Also, the iVN/Cbm-type projected mainly to the ipsilateral nodulus. Neurons of these types of axons showed different distribution within the MVN. The number of MF terminals of some vestibulocerebellar axons, iVN/Cbm-type axons in particular, and primary afferent axons were much smaller than observed in previously studied MF axons originating from major precerebellar nuclei and the spinal cord. The results demonstrated that a heterogeneous population of MVN neurons provided divergent MF inputs to the cerebellum. The cVN/Cbm- and iVN/Cbm-types indicate that some excitatory neuronal circuits within the vestibular nuclei supply their collaterals to the vestibulocerebellum as MFs.     

Omentin-1 attenuates adipose tissue inflammation via restoration of TXNIP/NLRP3 signaling in high-fat diet-induced obese mice

Omentin-1 is an adipokine expressed by the adipose tissue and is reduced in obesity. This study was designed to calculate the protective efficiency and mechanism of omentin-1 against inflammation of the adipose tissue in obese mice. A transgenic mouse model with omentin-1 protein overexpression was established by crossing omentin-1 transgenic mice with Fabp4-Cre mice. Obesity was induced in the mice by feeding them a high-fat diet for 10 weeks. Fabp4-Cre-mediated overexpression of omentin-1 significantly increased serum omentin-1 level, serum anti-inflammatory factor levels, and expression of M2-specific mRNAs; inhibited body weight and adipose tissue weight gain; improved glucose tolerance, insulin tolerance, and insulin sensitivity; decreased serum levels of insulin and proinflammatory factors, adipocyte size, and expression of M1-specific mRNAs; suppressed macrophage infiltration; downregulated expression of proinflammatory factors; upregulated expression of anti-inflammatory factors; and inhibited thioredoxin-interacting protein (TXNIP)/NOD-like receptor 3 (NLRP3) signaling in the adipose tissue of obese mice. An NLRP3 inhibitor (20 mg/kg MCC950) exhibited the same effects as overexpression of omentin-1. Pretreatment with omentin-1 inhibited lipopolysaccharide-induced inflammation via TXNIP/NLRP3 signaling in RAW 264.7 macrophages. These findings suggest that omentin-1 suppresses adipose tissue inflammation in obese mice, at least partly, via inhibiting the TXNIP/NLRP3 signaling pathway.     

紫柏凝胶通过调节ERK及P38/MAPK信号通路下调宫颈癌荷瘤裸鼠E6、E7蛋白表达研究

目的:观察ERK及P38/MAPK信号通路在紫柏凝胶影响宫颈癌裸鼠移植瘤致癌蛋白E6、E7表达中的作用。方法:体外培养Siha细胞,成功建立人宫颈癌荷瘤裸鼠模型,随机分为模型组,顺铂组(腹腔内注射0.5 ml顺铂,4 d1次),紫柏凝胶高、中、低剂量组(外用紫柏凝胶0.9428、0.4714、0.2357 g/kg,1 d1次),试验期28 d。称取瘤重并测量瘤体积,HE染色观察移植瘤组织病理学变化,免疫组化SP法检测瘤体中的p-p38、p-ERK、E6及E7蛋白表达水平。结果:紫柏凝胶各组的裸鼠肿瘤体积均明显小于模型组(P<0.05),高、中、低剂量组抑瘤率分别为36.23%、31.24%和14.94%。HE染色紫柏凝胶各剂量组移植瘤组织出现明显坏死样改变。与模型组比较,高、中剂量紫柏凝胶组瘤组织的E6、E7蛋白表达水平降低(P<0.05),同时p-ERK及p-p38蛋白水平明显下降(P<0.05)。结论:紫柏凝胶对HPV(+)宫颈癌Siha细胞裸鼠移植瘤的生长具有明显抑制作用,可下调致癌蛋白E6和E7的表达,其机制可能与抑制ERK及P38/MAPK信号通路有关。     

Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy

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Lycium barbarum polysaccharide-glycoprotein preventative treatment ameliorates aversive stimuli-induced depression

Previous studies have shown that Lycium barbarum polysaccharide,the main active component of Lycium barbarum,exhibits antiinflammatory and antioxidant effects in treating neurological diseases.However,the therapeutic action of Lycium barbarum polysaccharide on depression has not been studied.In this investigation,we established mouse models of depression using aversive stimuli including exposure to fox urine,air puff and foot shock and physical restraint.Concurrently,we administered 5 mg/kg per day Lycium barbarum polysaccharide-glycoprotein to each mouse intragastrically for the 28 days.Our results showed that long-term exposure to aversive stimuli significantly enhanced depressive-like behavior evaluated by the sucrose preference test and the forced swimming test and increased anxietylike behaviors evaluated using the open field test.In addition,aversive stimuli-induced depressed mice exhibited aberrant neuronal activity in the lateral habenula.Importantly,concurrent Lycium barbarum polysaccharide-glycoprotein treatment significantly reduced these changes.These findings suggest that Lycium barbarum polysaccharide-glycoprotein is a potential preventative intervention for depression and may act by preventing aberrant neuronal activity and microglial activation in the lateral habenula.The study was approved by the Jinan University Institutional Animal Care and Use Committee(approval No.20170301003) on March 1,2017.