Effect of Delta-9-Tetrahydrocannabinol on Mouse Resistance to Systemic Candida albicans Infection

Delta-9-tetrahydrocannabinol (Δ⁹-THC), the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ⁹-THC treatment on mouse resistance to systemic Candida albicans (C. albicans) infection. To determine the outcome of chronic Δ⁹-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ⁹-THC (16 mg/kg) in vehicle on days 1–4, 8–11 and 15–18. On day 19, mice were infected with 5×10⁵ C. albicans. We also determined the effect of chronic Δ⁹-THC (4–64 mg/kg) treatment on mice infected with a non-lethal dose of 7.5×10⁴ C. albicans on day 2, followed by a higher challenge with 5×10⁵ C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ⁹-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ⁹-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ⁹-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ⁹-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge.     

The biology of Lubricin: Near frictionless joint motion

Lubricin is a surface-active mucinous glycoprotein secreted in the synovial joint that plays an important role in cartilage integrity. In healthy joints, lubricin molecules coat the cartilage surface, providing boundary lubrication and preventing cell and protein adhesion. Arthropathy occurring in patients with joint trauma, inflammatory arthritis or genetically mediated lubricin deficiencies have insufficient lubricin to prevent damage to articular cartilage. Recent studies in lubricin null joints indicate that lubricin (Prg4) plays a role in preventing damage to the superficial zone and preservation of chondrocytes. Progress in the production of recombinant forms of lubricin and the successes of lubricin supplementation in small animal models identify rhPRG4 as a potential therapeutic for patients with transient lubricin deficiency in the setting of trauma or autoimmune arthritis.     

The Effect of Adriamycin Exposure on the Notochord of Mouse Embryos

The notochord has important structural and signaling properties during vertebrate development with key roles in patterning surrounding tissues, including the foregut. The adriamycin mouse model is an established model of foregut anomalies where exposure of embryos in utero to the drug adriamycin leads to malformations including oesophageal atresia and tracheoesophageal fistula. In addition to foregut abnormalities, treatment also causes branching, displacement, and hypertrophy of the notochord. Here, we explore the hypothesis that the notochord may be a primary target of disruption leading to abnormal patterning of the foregut by examining notochord position and structure in early embryos following adriamycin exposure. Treated (n = 46) and control (n = 30) embryos were examined during the crucial period when the notochord normally delaminates away from the foregut endoderm (6–28 somite pairs). Transverse sections were derived from the anterior foregut and analyzed by confocal microscopy following immunodetection of extracellular matrix markers E‐cadherin and Laminin. In adriamycin‐treated embryos across all stages, the notochord was abnormally displaced ventrally with prolonged attachment to the foregut endoderm. While E‐cadherin was normally detected in the foregut endoderm with no expression in the notochord of control embryos, treated embryos up to 24 somites showed ectopic notochordal expression indicating a change in characteristics of the tissue; specifically an increase in intracellular adhesiveness, which may be instrumental in structural changes, affecting mechanical and signaling properties. This is consistent with disruption of the notochord leading to altered signaling to the foregut causing abnormal patterning and congenital foregut malformations.     

IRM-2近交系小鼠对电离辐射抗性的研究

目的观察IRM-2小鼠对电离辐射的耐受性.方法分析测定了IRM-2小鼠对137Csγ射线的LD50及经4.0Gy137Csγ射线照射后不同时间外周血白细胞、骨髓有核细胞总数、骨髓细胞DNA含量和脾结节的变化,并与亲代小鼠ICR和615进行了比较.结果用不同剂量的137Csγ射线照射后,IRM-2小鼠对γ射线的LD50比ICR和615小鼠分别高1.73～1.57Gy和1.44Gy;外周血白细胞数和骨髓有核细胞总数、骨髓细胞DNA含量下降的幅度小且恢复得快;CFU-S的增加也较ICR和615小鼠明显.结论IRM-2小鼠比一般的纯系和杂交品系小鼠具有更强的辐射抗性.     

不同品系小鼠对代谢性高尿酸血症造模的影响

目的:分别以昆明种小鼠及ICR、C57BL/6J小鼠为研究对象,比较在复制高尿酸血症模型时可能的小鼠品系差异,并通过降尿酸药物别嘌呤醇与非布索坦验证选择降尿酸药物筛选时选用不同品系动物造模的影响。方法:采用不同剂量次黄嘌呤腹腔注射联用尿酸酶抑制剂氧嗪酸钾皮下注射给药,测定不同造模时段各品系小鼠血清尿酸值。结果:ICR、C57BL/6J小鼠对高尿酸血症造模耐受显著高于昆明种小鼠,在腹腔注射次黄嘌呤500mg/kg,皮下注射氧嗪酸钾300mg/kg时,才可获得稳定的可用于药物筛选的高尿酸血症模型。结论:选择高尿酸血症在体模型时,昆明种小鼠灵敏度高于ICR小鼠以及近交系的C57BL/6J小鼠。     

高浓度葡萄糖对昆明小鼠早期胚胎发育的影响

建立昆明小鼠受孕模型,分离并体外培养胚胎细胞.检测了各培养浓度下的细胞增殖、分化与凋亡.胚胎细胞在0.2mmol/L和5.56mmol/L葡萄糖浓度的KSOM培养基中能正常发育和孵化;而在浓度为15.56mmol/L和25.56mmol/L葡萄糖培养基中胚胎发育和孵化均受到损害(P<0.005),且总细胞数和内细胞团细胞数也明显减少(P<0.01),但其细胞凋亡率与0.2mmol/L和5.56mmol/L葡萄糖浓度下胚胎细胞凋亡率无显著性差异(P>0.05).随着葡萄糖浓度的增高,胚泡总的表面积无明显变化,但胚胎细胞密度呈增加趋势.高血糖对早期胚胎的发育具有毒性作用,提示高糖可能导致妊娠合并糖尿病患者的流产和胎儿畸形率升高.     

谷胱甘肽在小鼠卵母细胞玻璃化冷冻中的作用

目的：观察谷胱甘肽在小鼠玻璃化冷冻中的保护性作用。方法：通过卵母细胞是否玻璃化冷冻及是否添加GSH处理,将小鼠卵母细胞分为4组。检测卵母细胞内GSH浓度、ROS水平,以及通过彗星实验量化OTM值检测DNA碎片的生成。结果：在对照组、冷冻组、GSH处理组和GSH处理冷冻组细胞内GSH浓度分别为8．95±1．26、4．36±0．96、9．27±1．05和8．18±0．89;ROS水平分别为47．5±4．23、64．2±5．69、44．5±3．25and49．9±7．62。通过GSH处理,玻璃化冷冻卵母细胞出现彗尾百分比显著低于未处理组,差异具有统计学意义;通过GSH处理,玻璃化冷冻卵母细胞OTM值低于未处理组,差异无统计学意义。结论：玻璃化冷冻使小鼠卵母细胞产生一定的氧化应激损伤,表现为细胞内GSH浓度下降,ROS水平上升,DNA碎片增加,GSH处理可以在一定程度上改善。     

金雀异黄素对小鼠红白血病细胞系MEL的抑制作用

选择小鼠红白血病细胞系MEL作为金雀异黄素 (genistein)的作用对象 ,以探讨其对MEL的抑制作用及其可能的作用机理 .MTT和生长曲线表明 ,金雀异黄素对MEL细胞具有很强的生长抑制作用 (半数最大抑制效应浓度IC50 为 7 12mg L) .流式细胞术显示 ,金雀异黄素能够使MEL细胞发生G2 M期阻滞 ,但是诱导MEL凋亡作用并不明显 .DNA凝胶电泳发现金雀异黄素能够造成MEL细胞DNA的损伤 .联苯胺染色显示金雀异黄素对MEL细胞具有很强的诱导分化作用 ,且这种作用是时间和剂量依赖性的 .RT PCR显示 ,金雀异黄素能够抑制MEL细胞中原癌基因c myc的表达 .生物流变学检测发现 :金雀异黄素作用后 ,MEL细胞表面电荷密度减少、渗透脆性增大、细胞最大变形能力下降     

不同品系小鼠对代谢性高尿酸血症造模的影响

目的：分别以昆明种小鼠及ICR、C57BL/6J小鼠为研究对象,比较在复制高尿酸血症模型时可能的小鼠品系差异,并通过降尿酸药物别嘌呤醇与非布索坦验证选择降尿酸药物筛选时选用不同品系动物造模的影响。方法：采用不同剂量次黄嘌呤腹腔注射联用尿酸酶抑制剂氧嗪酸钾皮下注射给药,测定不同造模时段各品系小鼠血清尿酸值。结果：ICR、C57BL/6J小鼠对高尿酸血症造模耐受显著高于昆明种小鼠,在腹腔注射次黄嘌呤500mg/kg,皮下注射氧嗪酸钾300mg/kg时,才可获得稳定的可用于药物筛选的高尿酸血症模型。结论：选择高尿酸血症在体模型时,昆明种小鼠灵敏度高于ICR小鼠以及近交系的C57BL/6J小鼠。     

热休克对小白鼠组织中抗氧化酶活性的影响

热休克诱导小白鼠心、肝、肾、肺、脑等组织细胞SOD活性非常显著或显著升高,其中主要诱导CuZn-SOD的生物合成;42℃诱导小白鼠各组织细胞CAT活性极显著下降,正常情况下,脑细胞几乎不存在CAT活性,42℃热休克20min诱导脑CAT活力升高;热休克亦诱导各组织cSH-Px活性变化,心、脑细胞GSH-Px极显著升高,对肺的影响较小。SOD、CAT、GSH-Px协同作用,维持机体正常生理机能。还探讨了热休克应答、热耐受能力的获得与抗氧化酶活性变化存在的对应关系。     

合生元益生菌冲剂对小鼠肠道菌群调节作用的研究

目的 研究合生无益生菌冲剂对小鼠肠道菌群的调节作用.方法 将小鼠分为阴性对照组、合生元益生菌冲剂组.阴性对照组灌服蒸馏水14 d,合生元益生菌冲剂组灌服1 g/kg·d剂量的台生元益生菌冲剂14 d,检测实验前后肠道菌群数量.结果 灌服后小鼠肠道菌群与灌服前比较,,双歧杆菌数量有显著性增加（P＜0.05）,肠杆菌、肠球菌、乳杆菌和产气荚膜梭菌数量有无显著性变化（P＞0.05）.结论 合生元益生菌冲剂对小鼠肠道菌群具有一定的调节作用.     

氧化胁迫在硝基苯致小鼠神经毒性中的作用

目的:探讨氧化胁迫在硝基苯致小鼠神经毒性中的作用。方法:用不同剂量的硝基苯对小鼠进行灌胃染毒,每天1次,共30d;用碱性羟胺比色法测定小鼠脑乙酰胆碱酯酶活性,用试剂盒检测脑抗氧化功能。结果:试验组小鼠的中毒症状随着染毒剂量的增加和时间的延长而越来越明显;乙酰胆碱酯酶活性降低;与对照组相比,脑各项抗氧化指标均表现出显著或极显著差异。结论:氧化胁迫在硝基苯发挥神经毒性过程中起重要作用。     

防止肌腱粘连及促进其愈合的研究进展

随着对肌腱愈合研究的不断深入和发展,预防肌腱粘连以及促进其愈合的方法越来越多。通过改进缝合方法、修复腱鞘或采用替代品、置入药物或药物薄膜及早期康复等治疗来有效预防肌腱粘连;通过重建腱鞘、药物、生长因子、基因干预等促进肌腱愈合。本文就近年来防止肌腱粘连及促进其愈合方面的研究予以综述。     

表皮生长因子对转化的小鼠成纤维细胞DNA拓扑异构酶活性的影响

我们用表皮生长因子对用氚标记的脱氧胸苷转化的C_3H_(10)T1/2 CL8细胞进行刺激,研究了表皮生长因子对该细胞胞浆及胞核内DNA拓扑异构酶活性的影响,结果发现,表皮生长因子可以使转化的小鼠成纤维细胞胞浆和胞核内的DNA拓扑异构酶活性增加。     

线粒体自噬影响胰岛素抵抗的作用及机制

胰岛素抵抗（IR）是诱发许多代谢疾病的关键因素,包括代谢综合征、非酒精性脂肪性肝病、动脉粥样硬化和2型糖尿病（T2DM）。随着相关代谢疾病日益增多,寻找新的治疗靶点迫在眉睫。线粒体自噬是一种选择性自噬,其通过清除受损和功能失调的线粒体以维持正常线粒体功能和能量代谢。研究发现,线粒体自噬在代谢疾病中有积极作用,线粒体自噬受到各种信号通路与信号分子调控而改善代谢疾病,如AMPK/ULK1、PINK1/Parkin信号通路以及BNIP3/Nix和FUNDC1等信号分子。本文阐述了线粒体自噬在胰岛素抵抗中的作用及调控机制,综述了近年的相关研究进展。     

The Relationship of Capsular-type of Staphylococcus epidermidis to Virulence and Induction of Resistance in the Mouse

Biochemical, immunological and morphological properties of mouse virulent Staphylococcus epidermidis strains ATCC-31432, SE-360 and SE-10 isolated from clinical specimens were compared. Heat-killed organisms and cell surface polysaccharides extracted from cell surface fractions induced resistance in mice only against challenge with the homologous strain. Hyperimmune rabbit serum prepared with these strains passively protected mice against challenge infection only with the homologous strain. Protective activity in immune sera was absorbed by homologous whole cell and cell surface polysaccharide, but not by heterologous organisms and cell surface polysaccharide. In agar diffusion tests, cell surface polysaccharides from strains ATCC-31432, SE-360 and SE-10 produced single precipitin lines only with the homologous antiserum. The outermost layer of ultra-thin sections of the three strains was labelled by homologous but not by heterologous ferritin-conjugated serum. Biochemical analysis of the cell surface polysaccharides showed that they were composed of hexosamine, glycerol, phosphorous, alanine, glycine and phenylalanine. The three strains ATCC-31432, SE-360 and SE-10 were regarded as different from each other. Thirteen of 300 fresh isolates of Staph. epidermidis randomly selected from human clinical specimens proved to be virulent for mice. With ATCC-31432, SE-360 and SE-10 tentatively designated as capsular-type I, type II and III, respectively, a majority of mouse virulent strains belonged to capsular-type II.