Signaling of endothelial cytoprotection in transplantation

A better knowledge of the processes by which endothelium can resist to cell death and adapt to injury by specific intracellular signaling pathways and dedicated protein regulation is a key step to understand how vascular inflammation/injury develops and how it is regulated. This review focuses on signaling pathways and molecular effectors that trigger the balance between endothelial cell activation and dysfunction. In addition to the canonical nuclear factor-κB (NF-κB), phosphatidyl inositol 3-kinase (PI-3K) and mitogen-activated protein kinases (MAPK) that orchestrated the inflammatory response and its termination we report here additive pathways such as Notch pathway and protein C/protease activated receptor (PAR) pathway that have been also reported to play a role in the control of EC activation and apoptosis. This review also provides an update of the characteristics of some established and novel protective molecules for the endothelium, identified in transplantation.     

The influence of varus and valgus deviation on patellar kinematics in healthy knees: An exploratory cadaver study

Background

Patellofemoral instability may lead to osteoarthritis, anterior knee pain, and patellar luxation. The purpose of this study was to conduct an exploratory investigation into the difference of patellar kinematics of healthy knees during extension/flexion cycles in neutral, varus and valgus alignment.

心理干预对冠脉综合征患者不良情绪的影响

目的探讨心理干预对冠脉综合征患者焦虑抑郁不良情绪的影响。方法将56例冠脉综合征患者随机分为2组,观察组27例,对照组29例,2组均给予心血管内科常规治疗。观察组在此基础上联合心理干预,观察6周,于心理干预前及干预2周、6周末采用焦虑自评量表、抑郁自评量表评定两组患者的焦虑抑郁状况。结果心理干预前2组患者焦虑自评量表、抑郁自评量表评分均无显著性差异(t=0.704和0.523,P>0.05),干预2周后观察组评分均显著低于对照组(t=2.077和2.081,P<0.05),干预6周末后观察组评分也均显著低于对照组(t=2.244和2.209,P<0.05)。结论心理干预能显著改善冠脉综合症患者治疗过程中的焦虑抑郁不良情绪,有利于提高患者的生活质量。     

956对夫妇外周血染色体核型与不良孕产史的关系

目的探讨不良孕产史与染色体核型异常的关系。方法取患者的外周血进行无菌培养、制片及G显带技术进行染色体核型分析。结果通过对956对夫妇染色体核型分析,发现异常核型209例,异常率为11.77%。其中臂间倒位13例,占6.22%;平衡易位28例,占13.40%;性染色体异常2例,占0.96%;染色体多态性163例,占异常总数的77.99%;其他异常3例,占1.43%。结论染色体异常以及多态性是导致不良孕产史的重要因素,因此,染色体核型分析应作为优生优育的常规检查,从而提高人口素质,降低先天性出生缺陷。     

Automatic bad channel detection in intracranial electroencephalographic recordings using ensemble machine learning

Objective

Intracranial electroencephalographic (iEEG) recordings contain “bad channels”, which show non-neuronal signals. Here, we developed a new method that automatically detects iEEG bad channels using machine learning of seven signal features.

Anti-apoptotic actions of vasopressin in H32 neurons involve MAP kinase transactivation and Bad phosphorylation

Vasopressin (VP) secreted within the brain modulates neuronal function acting as a neurotransmitter. Based on the observation that VP prevented serum deprivation-induced cell death in the neuronal cell line, H32, which expresses endogenous V1 receptors, we tested the hypothesis that VP has anti-apoptotic properties. Flow cytometry experiments showed that 10 nM VP prevented serum deprivation-induced cell death and annexin V binding. Serum deprivation increased caspase-3 activity in a time and serum concentration dependent manner, and VP prevented these effects through interaction with receptors of V1 subtype. The signaling pathways mediating the anti-apoptotic effect of VP involve mitogen activated protein (MAP) kinase and extracellular signal-regulated kinases (ERK), Ca²⁺/calmodulin dependent kinase (CaMK) and protein kinase C (PKC). Western blot analyses revealed time-dependent decreases of Bad phosphorylation and increases in cytosolic levels of cytochrome c following serum deprivation, effects which were prevented by 10 nM VP. These data demonstrate that activation of endogenous V1 VP receptors prevents serum deprivation-induced apoptosis, through phosphorylation-inactivation of the pro-apoptotic protein, Bad, and consequent decreases in cytosolic cytochrome c and caspase-3 activation. The data suggest that VP has anti-apoptotic activity in neurons and that VP may act as a neuroprotective agent in the brain.     

Melatonin-induced estrogen receptor α-mediated calbindin-D9k expression plays a role in H2O2-mediated cell death in rat pituitary GH3 cells

Abstract:  Calbindin-D9k (CaBP-9k) is a 9-kDa polypeptide possessing two calcium-binding sites that is expressed in the mammalian intestine, uterus, and pituitary gland. The factors regulating the expression of the estrogen receptor (ER) and CaBP-9k in the pituitary gland are currently unknown. In this study, we investigated whether the ER and CaBP-9k expression are regulated by melatonin during H₂O₂-induced cell death in rat pituitary GH3 cells. Cell survival increased by approximately 27–36% in H₂O₂ plus melatonin compared to H₂O₂ alone, and CaBP-9k expression was augmented by treatment with H₂O₂ plus melatonin. These results suggest that the increase in cell survival and the melatonin-induced CaBP-9k expression may play a role in protecting cells against H₂O₂-mediated cell death. This result is also consistent with the increase in CaBP-9k expression leading to rises in p-ERK and p-Bad (S112). Over-expression of CaBP-9k caused an increase in p-ERK. ERα expression was higher in H₂O₂ plus melatonin-treated cells compared to those treated with H₂O₂ alone, while ERβ expression was not. Also, ERα in the nuclear fraction increased in the presence of melatonin and decreased in the presence of ICI 182 780 or ICI 182 780 plus melatonin. The relative binding affinity of ERα for melatonin was higher than that of ERβ, suggesting that melatonin has the potential to preferentially bind ERα. In conclusion, these results indicate that melatonin may increase CaBP-9k expression through ERα.     

急性一氧化碳中毒大鼠BAD蛋白表达变化的研究

目的:研究急性一氧化碳中毒大鼠迟发性脑病模型中Bad蛋白在大鼠额叶皮质和海马区的表达变化情况。方法:选择取腹腔注射纯CO制备急性一氧化碳中毒与一氧化碳中毒迟发性脑病的大鼠模型。造模后分别于1、3、7、14、21d观察大鼠大脑皮质及海马区细胞的Bad蛋白的表达情况。结果:Bad蛋白表达在第1天表达明显,以后逐渐降低至染毒后21d,但仍高于对照组(p<0.01)。结论:Bad蛋白作为一种促凋亡因子表达活跃,可能是急性一氧化碳中毒迟发性脑病发生的病理机制之一。     

The serine-threonine kinase p90RSK is a new target of enzastaurin in follicular lymphoma cells

BACKGROUND AND PURPOSE

Follicular lymphoma is the second most common non-Hodgkin''s lymphoma and, despite the introduction of rituximab for its treatment, this disease is still considered incurable. Besides genetic alterations involving Bcl-2, Bcl-6 or c-Myc, follicular lymphoma cells often display altered B-cell receptor signalling pathways including overactive PKC and PI3K/Akt systems.

EXPERIMENTAL APPROACH

The effect of enzastaurin, an inhibitor of PKC, was evaluated both in vitro on follicular lymphoma cell lines and in vivo on a xenograft murine model. Using pharmacological inhibitors and siRNA transfection, we determined the different signalling pathways after enzastaurin treatment.

KEY RESULTS

Enzastaurin inhibited the serine-threonine kinase p90RSK which has downstream effects on GSK3β. Bad and p70S6K. These signalling proteins control follicular lymphoma cell survival and apoptosis; which accounted for the inhibition by enzastaurin of cell survival and its induction of apoptosis of follicular lymphoma cell lines in vitro. Importantly, these results were replicated in vivo where enzastaurin inhibited the growth of follicular lymphoma xenografts in mice.

CONCLUSIONS AND IMPLICATIONS

The targeting of p90RSK by enzastaurin represents a new therapeutic option for the treatment of follicular lymphoma.     

铜陵市3~6岁儿童口腔不良习惯调查分析

目的 了解铜陵市3~6岁儿童口腔不良习惯的发生情况。方法 采用整群抽样法,随机抽取铜陵市城区3243名3~6岁在园儿童,利用自行设计的调查问卷,对儿童家长进行口腔不良习惯的调查。结果 3243名3~6岁儿童中,有口腔不良习惯的儿童2147人,发生率66.2%;具有3项或3项以上口腔不良习惯121人,发生率3.73%。在各个分项中,以夜间磨牙的儿童872人最多,占26.88%;其次咬物(指甲、铅笔等)的儿童814人,占25.10%。结论 铜陵市3~6岁儿童多数有口腔不良习惯,且随着年龄的增长口腔不良习惯发生率增高。应加强儿童卫生健康教育及干预,帮助孩子养成良好的口腔习惯。