Role of mesenchymal-epithelial interactions in mammary gland development

The mammary gland is a hormone-target organ derived from epidermis and develops as a result of reciprocal mesenchymal-epithelial interactions. The induction of mammary differentiation from indifferent epidermal cells by mammary mesenchyme implies induction of the complement of hormone receptors characteristic of normal mammary epithelium in cells of the epidermis. Considering the facts that mammary epithelial differentiation is induced by mammary mesenchyme and that certain aspects of hormone response (androgen-induced mammary regression) are inextricably linked to mesenchymal-epithelial interactions, it is evident that the biology of the mammary gland arises from and is maintained via cell-cell interactions. As a corollary, perturbation of stromal-epithelial interactions in adulthood may play a role in mammary carcinogenesis and in turn may provide opportunities for differentiation therapy.     

Experimental vaccinia virus meningoencephalitis in adult albino mice: Virological,light microscopic and ultrastructural studies

Summary Adult NMRI mice were inoculated intracerebrally with 1.5–5×10² pfu of the neurovirulent strain Ma1 of vaccinia virus. The animals usually became diseased on day 3 and died on day 5 or 6 p.i. Infectivity assay studies on the mouse brains yielded a steeply rising viral titer comparable with that exhibited by several other so-called neurovaccinia strains after intracerebral inoculation. Histological studies revealed a patchy leptomeningitis most apparent over the basal brain surface. Mononuclear elements of varied size were the most common infiltrate cells in the meningitic lesions. These often showed a pronounced hemorrhagic and necrotizing character. In some places, the cellular infiltrates within the subarachnoid space extended along the perforating vessels into the superficial cerebral cortex. By electron microscopy, all essential stages of virus morphogenesis including the discharge of mature virions could be seen in numerous mononuclear phagocytes and adventitial cells. In contrast to this, no unequivocal neuroectodermal cell showed morphologic evidence of productive viral infection. Likewise, no endothelia or vascular myocytes were encountered which contained newly formed virus particles. However, alterations of the walls of blood vessels and signs of disturbed vascular permeability were a frequent finding in the meningeal foci of inflammation as well as in and around the track left by the inoculating needle. Another ultrastructural feature of the meningitic lesions was the widespread occurrence of degenerating or disintegrating infiltrate cells both infected and uninfected ones.The virologic and morphologic findings observed in this model of experimental vaccinia virus meningo-encephalitis are discussed with regard to data previously published by other authors. The propensity of strain Ma1 of vaccinia virus (and most probably of other so-called neurovaccinia strains) for replication in mesenchymal cells in particularly emphasized.     

试管地黄形成过程中形态发生的研究

目的 :研究试管地黄形成的形态发生过程 ,比较试管地黄与自然条件下生长的地黄在形态解剖上的异同。方法 :取离体条件下和自然条件下不同阶段形成的地黄块根 ,染色后制成石蜡切片 ,于显微镜下观察。结果与结论 :试管地黄在形态解剖方面与自然条件下生长的地黄具有一致性 ,说明试管地黄在诱导过程中未发生结构上的变化。     

滇重楼种子休眠破除及植株形态发生的研究

目的:在无菌培养条件下探讨植物激素对滇重楼种子休眠破除及植株形态发生的影响.方法:以滇重楼成熟种子为试验材料,在无菌培养条件下采用正交试验设计研究赤霉素(GA3)、玉米素核苷(ZR)、吲哚乙酸(IAA)及活性炭(AC)对滇重楼种子休眠破除的影响,并对无菌萌发过程中植株形态发生进行观察.结果:滇重楼种子无菌培养过程中种子萌动的最佳配比是GA3-ZR-IAA-AC(1.0 mg·L-1∶1.0 mg·L-1∶0.1 mg·L-1∶0.5 g·L-1),种子萌动率达80.00％,4种因子对滇重楼种子萌动率作用大小为IAA＞ GA3＞ZR ＞AC;滇重楼种子无菌培养过程中种子萌发的最佳配比是GA3-ZR-IAA-AC(1.0 mg·L-1∶1.0 mg·L-1∶0.1 mg·L-1∶0.5 g·L-1),种子萌发率达66.66％,4种因子对滇种楼种子发芽率作用大小为AC＞IAA ＞ZR＞GA3.结论:培养基添加植物激素GA,ZR,IAA,AC对滇重楼种子休眠破除、种子萌动及萌发有重要影响.     

Role of site-directed mutagenesis and adjuvants in the stability and potency of anthrax protective antigen

Anthrax is a zoonotic infection caused by the gram-positive, aerobic, spore-forming bacterium Bacillus anthracis. Depending on the origin of the infection, serious health problems or mortality is possible. The virulence of B. anthracis is reliant on three pathogenic factors, which are secreted upon infection: protective antigen (PA), lethal factor (LF), and edema factor (EF). Systemic illness results from LF and EF entering cells through the formation of a complex with the heptameric form of PA, bound to the membrane of infected cells through its receptor. The currently available anthrax vaccines have multiple drawbacks, and recombinant PA is considered a promising second-generation vaccine candidate. However, the inherent chemical instability of PA through Asn deamidation at multiple sites prevents its use after long-term storage owing to loss of potency. Moreover, there is a distinct possibility of B. anthracis being used as a bioweapon; thus, the developed vaccine should remain efficacious and stable over the long-term. Second-generation anthrax vaccines with appropriate adjuvant formulations for enhanced immunogenicity and safety are desired. In this article, using protein engineering approaches, we have reviewed the stabilization of anthrax vaccine candidates that are currently licensed or under preclinical and clinical trials. We have also proposed a formulation to enhance recombinant PA vaccine potency via adjuvant formulation.     

长期应用糖皮质激素对新生大鼠肺泡形态结构及IGFBP-2的影响

目的:探讨长期应用糖皮质激素 (ICSs) 对新生大鼠肺形态结构及其对肺内胰岛素样生长因子结合蛋白2 (IGFBP-2) 表达的影响?方法:新生SD大鼠48只随机分为3组:对照 (CONT) 组 (雾化吸入生理盐水);雾化吸入布地奈德 (BUD) 组;腹腔注射地塞米松 (DEX) 组?每个干预组内设7 d给药组与14 d给药组?大鼠5日龄时开始干预,各组在连续给药7?14 d 后,测量大鼠体重及肺组织重量,计算肺系数,通过肺组织形态学分析评估肺发育程度,应用蛋白免疫印迹技术 (WB) 检测IGFBP-2在肺组织中的表达?结果:① 大鼠体重及肺系数:BUD组与CONT组体重间差异无统计学意义 (P > 0.05),但DEX组体重较CONT组明显下降 (P < 0.01)?BUD组肺系数低于CONT组 (P < 0.01)?给药14 d后,DEX组肺系数与CONT组间无统计学差异 (P > 0.05);② 肺组织形态学:BUD组?DEX组肺泡囊数量较CONT组减少 (P < 0.01),间隔变薄 (P < 0.01),囊腔增大 (P < 0.05),BUD组?DEX组肺泡形态学指标间无统计学差异(P > 0.05);③肺组织IGFBP-2蛋白表达:IGFBP-2在BUD组?DEX组表达强于CONT组?结论:长期应用糖皮质激素可抑制新生大鼠肺泡化过程,该现象可能与糖皮质激素上调IGFBP-2在肺组织中的表达有关?     

Melatonin and serotonin: Mediators in the symphony of plant morphogenesis

Melatonin and serotonin are important signaling and stress mitigating molecules that play important roles across growth and development in plants. Despite many well‐documented responses, a systematic investigation of the entire metabolic pathway (tryptophan, tryptamine, and N‐acetylserotonin) does not exist, leaving many open questions. The objective of this study was to determine the responses of Hypericum perforatum (L.) to melatonin, serotonin, and their metabolic precursors. Two well‐characterized germplasm lines (#4 and 112) created by mutation and a haploid breeding program were compared to wild type to identify specific responses. Germplasm line 4 has lower regenerative and photosynthetic capacity than either wild type or line 112, and there are documented significant differences in the chemistry and physiology of lines 4 and 112. Supplementation of the culture media with tryptophan, tryptamine, N‐acetylserotonin, serotonin, or melatonin partially reversed the regenerative recalcitrance and growth impairment of the germplasm lines. Quantification of phytohormones revealed crosstalk between the indoleamines and related phytohormones including cytokinin, salicylic acid, and abscisic acid. We hypothesize that melatonin and serotonin function in coordination with their metabolites in a cascade of phytochemical responses including multiple pathways and phytohormone networks to direct morphogenesis and protect photosynthesis in H. perforatum.     

Chemical screening identifies filastatin,a small molecule inhibitor of Candida albicans adhesion,morphogenesis, and pathogenesis

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.     

The role of Kupffer cells in the morphogenesis of nonalcoholic steatohepatitis – ultrastructural findings. The first report in pediatric patients

Abstract

Objective. Until now studies concerning the involvement of hepatic nonparenchymal cells (NPCs), particularly Kupffer cells/macrophages (KCs/MPs), in the pathogenesis of human nonalcoholic steatohepatitis (NASH) have been limited to adult patients; there are no similar reports referring to children. This study aimed to explore, based on ultrastructural analysis, the role of KCs/MPs in the morphogenesis of nonalcoholic steatohepatitis (NASH) in children. Material and methods. Ultrastructural investigations of KCs were conducted on liver bioptates obtained from 10 children, aged 2–14 years, with clinicopathologically diagnosed NASH. Bioptatic material was fixed in solution of paraformaldehyde and glutaraldehyde in cacodylate buffer, routinely processed for transmission-electron microscopic analysis and examined using an Opton EM microscope. Results. The current ultrastructural study revealed within the hepatic sinusoids the presence of numerous enlarged KCs with increased phagocytic activity, which reduced or blocked vascular lumen. Interestingly, the activated KCs not only contained primary and secondary lysosomes, altered mitochondria, and well-developed Golgi apparatus, but also absorbed fragments of erythrocytes. Such macrophages were frequently seen very close to the transformed hepatic stellate cells (T-HSCs) and progenitor/oval cells. Intensive fibrosis was observed in the vicinity of activated KCs/MPs. Bundles of collagen fibers were seen directly adhering to these cells and to other NPCs, especially T-HSCs. Conclusions. KCs are involved in the morphogenesis and development of pediatric NASH. Engulfment of erythrocytes by hepatic macrophages may lead to the accumulation of iron derived from hemoglobin in liver and play a role in triggering the generation of oxidative stress in the disease course.