Membrane-associated mucins of the ocular surface: New genes,new protein functions and new biological roles in human and mouse

The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world. However, it is increasingly appreciated that MAMs also function as cell surface receptors that transduce information from the outside to the inside of the cell. A number of excellent review articles have provided perspective on the field as it has progressed since 1987, when molecular cloning of the first MAM was reported. The current article provides an update for the ocular surface, placing it into the broad context of findings made in other organ systems, and including new genes, new protein functions and new biological roles. We discuss the epithelial tissue-equivalent with mucosal differentiation, the key model system making these advances possible. In addition, we make the first systematic comparison of MAMs in human and mouse, establishing the basis for using knockout mice for investigations with the complexity of an in vivo system. Lastly, we discuss findings from human genetics/genomics, which are providing clues to new MAM roles previously unimagined. Taken together, this information allows us to generate hypotheses for the next stage of investigation to expand our knowledge of MAM function in intracellular signaling and roles unique to the ocular surface.     

临床护理路径在腹腔镜下全子宫切除术中的运用

目的探讨临床护理路径在腹腔镜下全子宫切除术中的运用效果。方法将60例在腹腔镜下全子宫切除术的患者按随机数字表法分为对照组和观察组,各30例。其中对照组给予常规护理,观察组按临床护理路径实施护理,比较两组患者术后排气时间、下床时间、住院时间、护理缺陷发生率以及患者满意度。结果观察组患者术后下床时间、排气时间及住院时间均短于对照组(P<0.05);观察组患者的护理缺陷发生率低于对照组(P<0.05);观察组患者的护理满意度高于对照组(P<0.05)。结论临床护理路径有助于护理操作的流程化和规范化,提高工作效率,缩短患者住院时间,降低护理缺陷发生率,提高患者满意度。     

以彝族药痛舒胶囊开发为例探索民族药创新发展路径＊

民族药是我国传统医药的重要组成部分，对中华民族的繁衍生息做出了巨大贡献。民族药在民间的应用实践十分丰富，是极为重要的新药开发来源，但由于在开发研究及产业化过程中存在基础研究薄弱、资源利用可持续性差、知识产权保护不足、市场意识不足等问题，阻碍了民族药的创新发展。本文以云南省药物研究所成功开发的彝族药痛舒胶囊为例，总结民族药开发实践经验，探讨民族药创新发展路径，为民族药的新药开发、产业化发展及国际化提供实践参考。     

支气管哮喘发作护理路径的实施效果

目的探究支气管哮喘发作护理路径的实施效果。方法选取笔者所在医院2018年4月—2019年4月期间收治的支气管哮喘发作患者72例纳入本次研究,随机分为两组各36例,对照组患者行常规护理,观察组患者行临床路径护理干预,对比两组患者哮喘控制率以及护理满意度。结果在哮喘控制率方面,观察组数据(97.22%)明显高于对照组,P<0.05;观察组护理满意度评分(92.56±5.41)分,显著优于对照组,P<0.05。结论在支气管哮喘发作中运用临床护理路径效果确切,可有效改善患者临床症状及预后,控制哮喘发作情况,提高患者生活质量,在临床上有较高的使用价值。     

The effect of interleukin 6 deficiency on myocardial signal transduction pathways activation induced by bacterial lipopolysaccharide in young and old mice

PurposeExaggerated release of proinflammatory mediators during sepsis contributes to inadequate vasodilatation and depressed myocardial contractility, which lead to development of shock and circulatory collapse. The aim of the study was to evaluate the effect of IL-6 and aging on activation of intracellular signaling pathways in the myocardium induced by bacterial lipopolysaccharide (LPS) administration.Material/methodsLPS was injected intraperitoneally to male 3- and 24-month old mice with systemic IL-6 gene knock-out (IL-6KO) and the reference strain (WT). LPS was given intraperitoneally in single low (0.1 mg/kg) or high (10 mg/kg) dose, or in two doses (0.1 + 10 mg/kg) with 24-h delay. The expression and phosphorylation of STAT3, ERK1/2, Akt1/2/3 proteins in the left ventricular myocardium was evaluated after 24 h using Western blotting.ResultsLow LPS dose induced higher STAT3 phosphorylation only in old IL-6KO mice, not affecting ERK1/2 and Akt1/2/3 phosphorylation in any group. High LPS dose upregulated STAT3 phosphorylation similarly in all groups, reduced ERK1/2 expression in young WT mice and upregulated Akt1/2/3 expression and phosphorylation in young IL-6KO mice. Pretreatment with low LPS dose attenuated phosphorylation of STAT3 in both old groups and phosphorylation of Akt1/2/3 in young IL-6KO group. Two-dose approach also significantly potentiated ERK1/2 phosphorylation in both old groups.ConclusionsObtained results show that IL-6 deficiency alters the activity of intracellular signaling pathways: JAK/STAT in old and Akt in young LPS-treated mice. This may indicate that lack of IL-6 attenuates Akt-related cytoprotective effect of pretreatment with low LPS dose in young but not in aged animals.     

Tumor-specific lytic path “hyperploid progression mediated death”: Resolving side effects through targeting retinoblastoma or p53 mutant

A major advance was made to reduce the side effects of cancer therapy via the elucidation of the tumor-specific lytic path “hyperploid progression-mediated death” targeting retinoblastoma (Rb) or p53-mutants defective in G1 DNA damage checkpoint. The genetic basis of human cancers was uncovered through the cloning of the tumor suppressor Rb gene. It encodes a nuclear DNA-binding protein whose self-interaction is regulated by cyclin-dependent kinases. A 3D-structure of Rb dimer is shown, confirming its multimeric status. Rb assumes a central role in cell cycle regulation and the “Rb pathway” is universally inactivated in human cancers. Hyperploidy refers to a state in which cells contain one or more extra chromosomes. Hyperploid progression occurs due to continued cell-cycling without cytokinesis in G1 checkpoint-defective cancer cells. The evidence for the triggering of hyperploid progression-mediated death in RB-mutant human retinoblastoma cells is shown. Hence, the very genetic mutation that predisposes to cancer can be exploited to induce lethality. The discovery helped to establish the principle of targeted cytotoxic cancer therapy at the mechanistic level. By triggering the lytic path, targeted therapy with tumor specificity at the genetic level can be developed. It sets the stage for systematically eliminating side effects for cytotoxic cancer therapy.     

Comparison of the Torsional Resistance of 4 Different Glide Path Instruments

IntroductionThe present study aimed to compare the torsional strength of the initial files of the Mtwo (VDW, Munich, Germany) and novel Rotate systems (VDW, Munich, Germany) with the ProGlider (Dentsply Sirona, Ballaigues, Switzerland) and R-Pilot (VDW) glide path instruments.MethodsThe Mtwo (10/.04), ProGlider (16/.02), R-Pilot (12.5/.04), and Rotate (15/.04) glide path files were compared regarding their torsional strength, which was tested using a specially designed test device (N = 20). The data obtained were statistically analyzed at 5% significance level using 1-way analysis of variance and the post hoc Tukey test. The fragment surfaces and separated instruments were examined with ×50, ×100, and ×1000 magnification under a scanning electron microscope.ResultsThe R-Pilot group showed the highest torsional strength value among all groups (P < .05), whereas there was no significant difference between the torsional strength values of the Mtwo and ProGlider groups (P > .05). The Rotate group had the lowest torsional strength among all groups (P < .05). The Mtwo group showed the lowest angle of rotation among all groups (P < .05).ConclusionsAlthough the R-Pilot glide path file exhibited the highest torsional strength in all groups, Rotate showed the highest angle of rotation. Differences in torsional resistance of the instruments may be associated with their manufacturing methods and design features.     

Targeting autophagy in colorectal cancer: An update on pharmacological small-molecule compounds

Autophagy, an evolutionarily highly conserved cellular degradation process, plays the Janus role (either cytoprotective or death-promoting) in colorectal cancer, so the targeting of several key autophagic pathways with small-molecule compounds may be a new therapeutic strategy. In this review, we discuss autophagy-associated cell death pathways and key cytoprotective autophagy pathways in colorectal cancer. Moreover, we summarize a series of small-molecule compounds that have the potential to modulate autophagy-associated cell death or cytoprotective autophagy for therapeutic purposes. Taken together, these findings demonstrate the Janus role of autophagy in colorectal cancer, and shed new light on the exploitation of a growing number of small-molecule compounds to target autophagy in future cancer drug discovery.