Nitric oxide and carbon monoxide as possible retrograde messengers in hgippocampal long-term potentiation

We have been investigating the hypothesis that the membrane-permeant molecules nitric oxide (NO) and carbon monoxide(CO) may act as retrograde messengers during long-term potentiation (LTP). Inhibitors of either NO synthase or heme oxygenase, the enzyme that produces CO, blocked induction of LTP in the CA1 region of hippocampal slices. Brief application of either NO or CO to slices produced a rapid and long-lasting increase in the size of synaptic potentials if, and only if, the application occurred at the same time as weak tetanic stimulation of the presynaptic fibers. The long-term enhancement by NO or CO was spatially restricted to synapses from active presynaptic fibers and appeared to involve mechanisms utilized by LTP, occluding the subsequent induction of LTP by strong tetanic stimulation. The enhancement by No or CO was not blocked by the NMDA receptor blocker APV, suggesting that NO and CO act downstream for the NMDA receptor. In other systems, both NO and CO produce many of their effects by activation of soluble guanylyl cyclase nd cGMP-dependent protein kinase. An inhibitor of soluble guabylyl cyclase blocked the induction of normal LTP. Conversely, membrane-permeabel analog 8-Br-cGMP produced a rapid onset and long-lasting synaptic enhancement if, and only if, it was applied at the same time as weak presynaptic stimulation. Similarly, two inhibitors of cGMP-dependent protein kinase blocked the induction of normal LTP, and a selective activator of cGMP-dependent protein kinase produced activity-dependent long-lasting synaptic enhancement. 8-Br-cGMP also produced and activity-dependent, long-lasting increase in the amplitude of evoked synaptic current between pairs of hippocampal neurons in dissociated cell culture. In addition, 8-Br-cGMP, like NO, produced a long-lasting increase in the frequency of spontaneous miniature synaptic currents. These results are consistent with the hypothesis that NO and CO, either alone or in combination, serve as retrograde messengers that produce activity-dependent presynaptic enhancement, perhaps by stimulating soluble guanbylyl cyclase and cGMP-dependent protein kinase, during LTP in hippocampus. 1994 John Wiley & Sons, Inc.     

肝硬化食管胃静脉曲张患者门静脉血栓形成及内镜治疗后门脉高压性胃病加重的危险因素分析

摘要 目的：探讨肝硬化食管胃静脉曲张患者门静脉血栓形成及治疗后门脉高压性胃病加重的危险因素。方法：回顾性选择2019年1月至2023年12月来我院诊治的肝硬化食管胃静脉曲张患者102例,所有患者均行食管胃静脉曲张内镜下治疗,根据患者是否出现门静脉血栓将其分为两组,门静脉血栓组（n=48例）、非门静脉血栓者（54例）,对比两组的实验室检查、一般临床资料、影像学检查结果,使用多因素Logistic回归分析确定肝硬化食管胃静脉曲张门静脉血栓的危险因素。根据治疗后患者是否出现门脉高压性胃病加重。将102例患者分为门脉高压性胃病加重组与无门脉高压性胃病加重组组,对比两组的一般资料、实验室检查结果。多因素Logistic回归分析确定内镜治疗后门脉高压性胃病加重的危险因素。结果：内镜下食管静脉曲张门静脉血栓形成比例为47.06%（48/102）。单因素分析结果表明,门静脉血栓形成组的脾切除史、胃底硬化剂注射史、PLT、FIB、D2、门静脉主干内径、脾脏长度、脾脏厚度、脾静脉内径明显较无门静脉血栓形成高（P<0.05）;多因素Logistic回归分析表明,有脾切除史、D-二聚体、PLT、脾脏厚度、脾静脉内径增大是肝硬化食管胃静脉曲张患者门静脉血栓形成的危险因素（P<0.05）。肝硬化食管胃静脉曲张患者内镜治疗后门脉高压性胃病加重占比为29.41%（30/102）,单因素分析结果表明,门脉高压性胃病加重组与无门脉高压性胃病加重组的食管静脉曲张分级、Child-Pugh分级、Hp感染、门奇静脉断流史、门静脉主干内径、脾静脉内径对比有统计学意义（P<0.05）;多因素Logistic回归分析表明,食管静脉曲张分级重度、Child-Pugh分级C级、有Hp感染、有门奇静脉断流史是肝硬化食管胃静脉曲张内镜治疗后门脉高压性胃病加重的危险因素（P<0.05）。结论：有脾切除史、D-二聚体、PLT、脾脏厚度、脾静脉内径升高是肝硬化食管胃静脉曲张门静脉血栓形成的危险因素,食管静脉曲张分级重度、Child-Pugh分级C级、有Hp感染、有门奇静脉断流史是内镜治疗肝硬化食管静脉曲后张门脉高压性胃病加重的危险因素。     

Anterograde and Retrograde Regulation of Nuclear Genes Encoding Mitochondrial Proteins during Growth,Development, and Stress

Mitochondrial biogenesis and function in plants require the expression of over 1000 nuclear genes encoding mitochondrial proteins （NGEMPs）. The expression of these genes is regulated by tissue-specific, developmental, internal, and external stimuli that result in a dynamic organelle involved in both metabolic and a variety of signaling processes. Although the metabolic and biosynthetic machinery of mitochondria is relatively well understood, the factors that regu- late these processes and the various signaling pathways involved are only beginning to be identified at a molecular level. The molecular components of anterograde （nuclear to mitochondrial） and retrograde （mitochondrial to nuclear） signaling pathways that regulate the expression of NGEMPs interact with chloroplast-, growth-, and stress-signaling pathways in the cell at a variety of levels, with common components involved in transmission and execution of these signals. This positions mitochondria as important hubs for signaling in the cell, not only in direct signaling of mitochondrial function per se, but also in sensing and/or integrating a variety of other internal and external signals. This integrates and optimizes growth with energy metabolism and stress responses, which is required in both photosynthetic and non-photosynthetic cells.     

IF1 reprograms energy metabolism and signals the oncogenic phenotype in cancer

Comment on: Formentini L, et al. Mol Cell 2012; 45:731-42.     

Expression of the nuclear gene TaF(A)d is under mitochondrial retrograde regulation in anthers of male sterile wheat plants with timopheevii cytoplasm

Alterations of mitochondrial-encoded subunits of the F_oF₁-ATPsynthase are frequently associated with cytoplasmic male sterility(CMS) in plants; however, little is known about the relationshipof the nuclear encoded subunits of this enzyme with CMS. Inthe present study, the full cDNA of the gene TaF_Ad that encodesthe putative F_Ad subunit of the F_oF₁-ATP synthase was isolatedfrom the wheat (Triticum aestivum) fertility restorer ‘2114’for timopheevii cytoplasm-based CMS. The deduced 238 amino acidpolypeptide is highly similar to its counterparts in dicotsand other monocots but has low homology to its mammalian equivalents.TaF_Ad is a single copy gene in wheat and maps to the short armof the group 6 chromosomes. Transient expression of the TaF_Ad–GFPfusion in onion epidermal cells demonstrated TaF_Ad's mitochondriallocation. TaF_Ad was expressed abundantly in stem, leaf, anther,and ovary tissues of 2114. Nevertheless, its expression wasrepressed in anthers of CMS plants with timopheevii cytoplasm.Genic male sterility did not affect its expression in anthers.The expression of the nuclear gene encoding the 20 kDa subunitof F_o was down-regulated in a manner similar to TaF_Ad in theT-CMS anthers while that of genes encoding the 6 kDa subunitof F_o and the subunit of F₁ was unaffected. These observationsimplied that TaF_Ad is under mitochondrial retrograde regulationin the anthers of CMS plants with timopheevii cytoplasm. Key words: CMS, F_Ad subunit, F_oF₁-ATP synthase, retrograde regulation, wheat Received 8 October 2007; Revised 9 January 2008 Accepted 28 January 2008     

鼻窦内镜术治疗鼻窦炎合并鼻息肉的疗效及对鼻腔通气和嗅觉功能的影响

目的:探讨鼻窦内镜术治疗鼻窦炎合并鼻息肉的临床疗效及对鼻腔通气和嗅觉功能的影响。方法:选取2014年1月至2016年6月我院收治的鼻窦炎合并鼻息肉患者80例。根据随机数字表法分为观察组和对照组,各40例。对照组给予传统摘除术治疗,观察组则行鼻窦内镜术治疗。比较两组临床疗效以及治疗前、治疗后3个月症状评分、鼻气道总阻力、嗅觉功能评分。结果:观察组治疗总有效率为95.00%,显著高于对照组的77.50%(P0.05)。治疗前两组患者鼻塞、脓涕、嗅觉障碍、疼痛及总症状评分比较无统计学差异(P0.05),治疗后3个月两组患者鼻塞、脓涕、嗅觉障碍、疼痛及总症状评分均低于治疗前,且观察组患者鼻塞、脓涕、嗅觉障碍、疼痛及总症状评分低于对照组(P0.05)。治疗前两组患者鼻气道总阻力、嗅觉功能评分比较无统计学差异(P0.05),治疗后3个月两组患者鼻气道总阻力、嗅觉功能评分均低于治疗前,且观察组低于对照组(均P0.05)。结论:鼻窦内镜术治疗鼻窦炎合并鼻息肉有利于改善患者临床症状,促进患者嗅觉功能以及鼻腔通气的恢复,是治疗鼻窦炎合并鼻息肉的有效方法。