抗病毒胶囊对豚鼠生殖器疱疹模型宫颈上皮、神经节及大脑皮质的影响

【目的】探讨抗病毒胶囊治疗生殖器疱疹的作用机理。【方法】豚鼠24只,随机分为4组,分别为模型对照组、抗病毒1号组、抗病毒2号组及阿昔洛韦组,复制生殖器疱疹模型后4d分别给予相应的药物,模型组给予等容量生理盐水,连续9d给药后,取大脑组织、脊神经节、宫颈上皮进行透射电镜观察。【结果】在模型组的脊神经节中发现乙型单纯疱疹病毒(HSV-2)颗粒,大脑皮质、宫颈上皮未见HSV-2存在,各治疗组脊神经节病毒颗粒数量较模型组减少,细胞器的损伤程度减轻;与无病毒颗粒标本比较,有病毒颗粒标本各细胞器的损伤较重。【结论】抗病毒胶囊对豚鼠生殖器疱疹模型动物的病理改变有治疗作用,其机理可能是通过抑制HSV在体内的活动状态,并佐证了HSV-2在脊神经节中潜伏的观点。     

High-mobility group box 1 protein orchestrates responses to tissue damage via inflammation,innate and adaptive immunity,and tissue repair

A single protein, HMGB1, directs the triggering of inflammation, innate and adaptive immune responses, and tissue healing after damage. HMGB1 is the best characterized damage-associated molecular pattern (DAMP), proteins that are normally inside the cell but are released after cell death, and allow the immune system to distinguish between antigens that are dangerous or not. Notably, cells undergoing severe stress actively secrete HMGB1 via a dedicated secretion pathway: HMGB1 is relocated from the nucleus to the cytoplasm and then to secretory lysosomes or directly to the extracellular space. Extracellular HMGB1 (either released or secreted) triggers inflammation and adaptive immunological responses by switching among multiple oxidation states, which direct the mutually exclusive choices of different binding partners and receptors. Immune cells are first recruited to the damaged tissue and then activated; thereafter, HMGB1 supports tissue repair and healing, by coordinating the switch of macrophages to a tissue-healing phenotype, activation and proliferation of stem cells, and neoangiogenesis. Inevitably, HMGB1 also orchestrates the support of stressed but illegitimate tissues: tumors. Concomitantly, HMGB1 enhances the immunogenicity of mutated proteins in the tumor (neoantigens), promoting anti-tumor responses and immunological memory. Tweaking the activities of HMGB1 in inflammation, immune responses and tissue repair could bring large rewards in the therapy of multiple medical conditions, including cancer.     

The developing oligodendrocyte: key cellular target in brain injury in the premature infant

Brain injury in the premature infant, a problem of enormous importance, is associated with a high risk of neurodevelopmental disability. The major type of injury involves cerebral white matter and the principal cellular target is the developing oligodendrocyte. The specific phase of the oligodendroglial lineage affected has been defined from study of both human brain and experimental models. This premyelinating cell (pre-OL) is vulnerable because of a series of maturation-dependent events. The pathogenesis of pre-OL injury relates to operation of two upstream mechanisms, hypoxia-ischemia and systemic infection/inflammation, both of which are common occurrences in premature infants. The focus of this review and of our research over the past 15-20 years has been the cellular and molecular bases for the maturation-dependent vulnerability of the pre-OL to the action of the two upstream mechanisms. Three downstream mechanisms have been identified, i.e., microglial activation, excitotoxicity and free radical attack. The work in both experimental models and human brain has identified a remarkable confluence of maturation-dependent factors that render the pre-OL so exquisitely vulnerable to these downstream mechanisms. Most importantly, elucidation of these factors has led to delineation of a series of potential therapeutic interventions, which in experimental models show marked protective properties. The critical next step, i.e., clinical trials in the living infant, is now on the horizon.     

Targeting ER stress induced apoptosis and inflammation in cancer

Disturbance in the folding capacity of the endoplasmic reticulum (ER), caused by a variety of endogenous and exogenous insults, prompts a cellular stress condition known as ER stress. ER stress is initially shaped to re-establish ER homeostasis through the activation of an integrated intracellular signal transduction pathway termed as unfolded protein response (UPR). However, when ER stress is too severe or prolonged, the pro-survival function of the UPR turns into a toxic signal, which is predominantly executed by mitochondrial apoptosis. Moreover, accumulating evidence implicates ER stress pathways in the activation of various ‘classical’ inflammatory processes in and around the tumour microenvironment. In fact, ER stress pathways evoked by certain conventional or experimental anticancer modalities have been found to promote anti-tumour immunity by enhancing immunogenicity of dying cancer cells. Thus, the ER functions as an essential sensing organelle capable of coordinating stress pathways crucially involved in maintaining the cross-talk between the cancer cell’s intracellular and extracellular environment. In this review we discuss the emerging link between ER stress, cell fate decisions and immunomodulation and the potential therapeutic benefit of targeting this multifaceted signaling pathway in anticancer therapy.     

Multidisciplinary assessment of children with deficits relating to attention, motor activity and perception: evaluation of the ANSER model

This study describes a process for multidisciplinary assessment of children having deficits in attention, motor activity and perception (DAMP) with an evaluation of that process based on the opinions of parents, teachers and team members. The process named the 'ANSER model' consists of six steps (I to VI) conducted over a 2-month period and a follow-up 2 years later (step VII). Parents and teachers are fully involved early in the process and their participation is considered essential for a good result. Particular consideration is given to directly helping a child understand him/herself and become aware of his/her own difficulties. Strategies to overcome those difficulties are developed together with the child, the parents and the teacher. A specific aspect of the assessment is the aim to provide therapy through discussion of the questions, thoughts and feelings evoked during, and by the process. The expectations of parents and teachers regarding the assessment, and their completion of six steps of the process were ascertained from questionnaires. A large majority of both parents and teachers had high expectations of the assessment. Slightly more parents than teachers were convinced of its necessity. Their expectations were satisfied. Parents, teachers and team members emphasized the importance of the participation of parents and teachers in the process. The average time required for a complete assessment according to the process and including the work of all the specialists was 33 hours.     

Follicular Dendritic Cell Activation by TLR Ligands Promotes Autoreactive B Cell Responses

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