TAPP analogs containing β3‐homo‐amino acids: synthesis and receptor binding

β‐Amino acids containing α,β‐hybrid peptides show great potential as peptidomimetics. In this paper, we describe the synthesis and affinity to μ‐opioid and δ‐opioid receptors of α,β‐hybrids, analogs of the tetrapeptide Tyr‐ d ‐Ala‐Phe‐Phe‐NH₂ (TAPP). Each amino acid was replaced with an l ‐ or d ‐β³‐h‐amino acid. All α,β‐hybrids of TAPP analogs were synthesized in solution and tested for affinity to μ‐opioid and δ‐opioid receptors. The analog Tyr‐β³h‐ d ‐Ala‐Phe‐PheNH₂ was found to be as active as the native tetrapeptide. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

腹腔镜下经腹腹膜前疝修补术与李金斯坦疝无张力修补术治疗老年腹股沟疝患者的疗效对比分析

摘要 目的：对比腹腔镜下经腹腹膜前疝修补术（TAPP）和李金斯坦（Lichtenstein）疝无张力修补术两种手术方式治疗老年腹股沟疝患者的疗效。方法：收集2018年8月-2020年7月于上海中医药大学附属岳阳中西医结合医院甲疝外科治疗的118例老年(≥60岁)腹股沟疝患者的临床资料进行回顾性分析,根据不同的手术方法分组,68例患者行TAPP作为TAPP组,50例患者行Lichtenstein疝无张力修补术作为Lichtenstein组。比较两组患者手术时间、术中出血量、术后切口视觉模拟量表（VAS）评分、排气时间、住院时间及术后近远期并发症发生率。结果：两组患者手术时间比较无显著差异（P＞0.05）;TAPP组患者术中出血量、排气时间和住院时间均显著低于Lichtenstein组（P＜0.05）;TAPP组患者术后不同时点切口VAS评分均显著低于Lichtenstein组（P＜0.05）;TAPP组患者近期并发症发生率显著低于Lichtenstein组（P＜0.05）;两组患者远期并发症发生率比较无显著差异（P＞0.05）。结论：与Lichtenstein疝无张力修补术比较,TAPP是治疗老年腹股沟疝患者安全有效的手术方法,可减轻患者术后疼痛感,患者恢复更快,并发症发生率更低,值得推广及应用。     

TAPP与TEP治疗成人腹股沟疝的效果及对预后恢复的影响

摘要 目的：对比经腹腔腹膜前疝修补术（TAPP）与完全腹膜外疝修补术（TEP）治疗成人腹股沟疝的效果及对预后恢复的影响。方法：选取2018年3月至2021年5月期间本院收治的80例腹股沟疝成人患者为研究对象,按照随机数表法将其分为TAPP组（n=38）和TEP组（n=42）,分别给予TAPP、TEP治疗。对比两组患者术中及术后情况（手术时间、术中出血量、术后住院时间、恢复正常活动时间、疼痛程度）,以及精索血管情况,统计术后并发症发生率。结果：TEP组手术时间、术后住院时间、恢复正常活动时间短于TAPP组,术中出血量少于TAPP组（P<0.05）;两组患者疼痛视觉模拟法（VAS）评分呈下降趋势,且差异具有统计学意义（P<0.05）,但各时间点VAS评分比较无明显差异（P>0.05）;术前,两组患者精索静脉管径及精索静脉血流速度比较无明显差异（P>0.05）,术后4周,两组患者精索静脉管径均增大,静脉血流速度均减小,但TEP组上述指标优于TAPP组（P<0.05）;TAPP组并发症发生率（7.89%）略低于TEP组（9.52%）,差异无统计学意义（t=0.066,P=0.797）。结论：TAPP、TEP治疗成人腹股沟疝安全性均良好,但TEP术后恢复更快,且对精索静脉的影响较小。     

High-affinity calcium-binding proteins in Escherichia coli

Crude extracts of Escherichia coli contain at least three heat stable proteins of Mr, 33,000, 47,000, and 60,000, which bind 45Ca2+ in buffers containing micromolar calcium and physiological salt concentrations. Fractions containing these proteins neither activated the calmodulin-dependent enzyme, NAD kinase, nor inhibited the activity of this enzyme in the presence of brain calmodulin. Radioimmunoassay of crude extracts for calmodulin indicated the presence of a calmodulin-like antigen. Crude extracts also contain proteins that interact with 2-trifluoromethyl-10H-(3'-aminopropyl)phenothiazine-Sepharose in a calcium-dependent manner, but proteins eluted from this resin did not bind calcium with high affinity.     

Novel nuclear translocation of inositol polyphosphate 4-phosphatase is associated with cell cycle,proliferation and survival

Inositol polyphosphate 4 phosphatase type I enzyme (INPP4A) has a well-documented function in the cytoplasm where it terminates the phosphatidylinositol 3-kinase (PI 3-K) pathway by acting as a negative regulator. In this study, we demonstrate for the first time that INPP4A shuttles between the cytoplasm and the nucleus. Nuclear INPP4A is enzymatically active and in dynamic equilibrium between the nucleus and cytoplasm depending on the cell cycle stage, with highest amounts detected in the nucleus during the G₀/G₁ phase. Moreover, nuclear INPP4A is found to have direct proliferation suppressive activity. Cells constitutively overexpressing nuclear INPP4A exhibit massive apoptosis. In human tissues as well as cell lines, lower nuclear localization of INPP4A correlate with cancerous growth. Together, our findings suggest that nuclear compartmentalization of INPP4A may be a mechanism to regulate cell cycle progression, proliferation and apoptosis. Our results imply a role for nuclear-localized INPP4A in tumor suppression in humans.     

Polarity complex proteins

The formation of functional epithelial tissues involves the coordinated action of several protein complexes, which together produce a cell polarity axis and develop cell-cell junctions. During the last decade, the notion of polarity complexes emerged as the result of genetic studies in which a set of genes was discovered first in Caenorhabditis elegans and then in Drosophila melanogaster. In epithelial cells, these complexes are responsible for the development of the apico-basal axis and for the construction and maintenance of apical junctions. In this review, we focus on apical polarity complexes, namely the PAR3/PAR6/aPKC complex and the CRUMBS/PALS1/PATJ complex, which are conserved between species and along with a lateral complex, the SCRIBBLE/DLG/LGL complex, are crucial to the formation of apical junctions such as tight junctions in mammalian epithelial cells. The exact mechanisms underlying their tight junction construction and maintenance activities are poorly understood, and it is proposed to focus in this review on establishing how these apical polarity complexes might regulate epithelial cell morphogenesis and functions. In particular, we will present the latest findings on how these complexes regulate epithelial homeostasis.