TRPV4在眼病理生理功能中的研究进展

瞬时受体电位香草醛受体4(TRPV4)是一种非选择性阳离子通道,负责感知细胞肿胀、温度、机械牵张、剪切应力和渗透压的变化,通过调节跨膜钙信号进而影响基因表达、细胞形态和细胞骨架等构建。TRPV4在全身广泛表达。在眼内,TRPV4在角膜、晶状体、睫状体、小梁网和视网膜等组织均有功能性表达。本文就TRPV4在眼内各个组织中的表达及生理病理功能方面进行阐述。随着TRPV4在眼部病理生理功能中的深入研究,TRPV4在角膜损伤修复、青光眼及视网膜血管生成方面可能成为潜在的新兴药物靶点,但仍需进一步的深入研究。

孵化后期热处理对肉雏鸡骨骼肌和肝脏温敏TRP离子通道及线粒体功能的影响

[目的]孵化后期热处理能够在一定程度上提高肉鸡的耐热性,而骨骼肌和肝脏线粒体功能及温敏瞬时电位(transient receptor potential,TRP)离子通道与机体耐热性密切相关。因此,本试验旨在研究孵化后期热处理(thermal manipulation,TM)对雏鸡骨骼肌和肝脏温敏TRP离子通道及线粒体功能的影响。[方法]选取240枚AA肉鸡种蛋随机分为3组(每组8个重复,每重复10枚种蛋):CON组,37.5℃孵化;TM1组,在孵化期第16~18天39.5℃热处理3 h·d^(-1);TM2组,在孵化期第16~18天41.5℃热处理3 h·d^(-1)。出雏后测定1日龄直肠温度,检测胸肌、腿肌和肝脏组织相关基因表达水平。[结果]与CON组相比,孵化后期热处理显著降低了1日龄雏鸡的直肠温度(P<0.01),TM1组雏鸡腿肌器官指数显著增加(P<0.05)。与CON组相比,TM2组雏鸡胸肌的avUCP基因表达水平显著降低(P<0.01),COXⅣ(P<0.05)、Tfam(P<0.01)、PGC1α(P<0.05)、ATP5B(P<0.01)和IDH3α(P<0.01)基因表达水平均显著增加,TRPV1、TRPV2和TRPV3基因表达水平均显著降低(P<0.05),SERCA1基因表达水平显著增加(P<0.01)。与CON组相比,TM2组雏鸡腿肌的avUCP基因表达水平显著降低(P<0.01),ATP5B基因表达水平显著增加(P<0.05);TM2组雏鸡肝脏组织的Tfam和SERCA1基因表达水平显著增加(P<0.05)。相关性分析结果显示,温敏TRP基因表达水平与线粒体经典产热基因avUCP和avANT表达呈正相关关系,与线粒体氧化磷酸化功能相关基因表达水平呈负相关关系。[结论]孵化后期热处理可通过降低1日龄雏鸡胸肌的温敏TRP基因和线粒体产热相关基因表达水平水平,增加线粒体生物发生及氧化磷酸化功能相关基因表达水平,引起线粒体热适应性变化。

TRP通道介导线粒体功能调控及其与心血管疾病关系研究进展

瞬时受体电位(transient receptor potential,TRP)通道是一类非选择性阳离子通道。近年来研究发现TRP通道与多种疾病有关,其中关于TRP通道通过线粒体功能调控参与相关心血管疾病机制的研究,正成为心血管疾病机制研究的热点之一。目前相关的文献主要集中在TRPV、TRPM和TRPC。本文主要就上述3种TRP通道在线粒体功能调节中的作用及其与心血管疾病的关系研究进展进行综述。

温和灸对IBS小鼠结肠Trp-kyn/5-HT代谢的调控机制研究

目的 观察温和灸干预对肠易激综合征模型小鼠结肠组织Trp-Kyn/5-HT限速酶表达及相关代谢物含量的影响,阐释艾灸治疗相关机制。方法 雄性清洁级C57BL/6J小鼠随机分为正常组、模型组、艾灸组、1-MT组、PCPA组,采用AWR评价小鼠内脏高敏感状态,采用LC-MS/MS法、免疫组织化学法及Real Time PCR法分别检测小鼠结肠组织Trp-Kyn/5-HT代谢物含量、Trp-Kyn/5-HT代谢限速酶IDO1、TPH1蛋白及m RNA表达。结果 与正常组相比,模型组小鼠30 mm Hg下AWR评分增高(P <0.05),结肠组织TPH1、IDO1蛋白及m RNA表达显著增高(P <0.05),5-HT含量及Kyn/Trp比值显著升高(P <0.05)。与模型组相比,艾灸组和1-MT组小鼠结肠组织IDO1蛋白表达明显下调(P <0.05),艾灸组和PCPA组小鼠结肠组织TPH1蛋白明显下调(P <0.05);1-MT组小鼠结肠组织IDO1 mRNA表达明显降低(P <0.05),PCPA组小鼠结肠组织TPH1 mRNA表达明显降低(P <0.05);艾灸组Kyn/Trp比值显著降低(P <0.05)。结论 温和灸可抑制IBS小鼠结肠过表达的IDO1及THP1蛋白活性,下调Kyn/Trp比值,可能是温和灸改善IBS模型小鼠内脏痛敏的机制之一。

经TRPV1/TRPA1⁃cGMP信号通路探究推拿对minor CCI模型大鼠背根神经节镇痛启动机制

目的探究三法三穴推拿手法对minor CCI模型大鼠的镇痛启动机制。方法将56只SD大鼠随机分为8组,即正常组、假手术组、模型1组、模型2组、推拿1组、推拿2组、推拿1+TRPV1拮抗剂组和推拿2+TRPA1拮抗剂组。模型组、推拿组和推拿+拮抗剂组建立minor CCI模型。推拿组和推拿+拮抗剂组在造模后7 d进行1次三法(点法、拨法、揉法)三穴(殷门穴、承山穴、阳陵泉穴)干预,模型组与假手术组进行抓握束缚,正常组不予干预。干预结束后各组先后进行机械缩足反射阈值(MWT)和热缩足反射潜伏期(TWL)测试不同性质痛觉的变化;采用硝酸还原酶法观察各组造模侧DRG中NO含量,ELISA、Western blot、qPCR等方法观察各组造模侧DRG内TRPV1/TRPA1⁃NO⁃cGMP⁃PKG信号通路蛋白、基因表达的变化情况。结果与模型组比较,行为学检测显示推拿1组、推拿2组MWT、TWL均有不同程度的延长;推拿1组、推拿2组、推拿1+TRPV1拮抗剂组、推拿2+TRPA1拮抗剂组DRG内TRPV1、TRPA1、NO、sGCβ、cGMP、PKG1的表达量均明显降低。结论推拿干预1次后即可有效改善周围神经损伤引起的温度觉、机械痛觉过敏症状;推拿可通过TRPV1/TRPA1⁃NO⁃cGMP⁃PKG信号通路发挥即刻镇痛和持续镇痛作用。

Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer

BACKGROUND Colorectal cancer(CRC)has a high incidence and mortality.Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of CRC.AIM To investigate the effect of indole-3-acetaldehyde(IAAD)on CRC.METHODS The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines(HCT116 and DLD-1).Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests.Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide.Invasiveness was investigated using the transwell assay.Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor(AhR)downstream genes.The PharmMapper,SEA,and SWISS databases were used to screen for potential target proteins of IAAD,and the core proteins were identified through the String database.RESULTS IAAD reduced tumorigenesis in a syngeneic mouse model.In CRC cell lines HCT116 and DLD1,IAAD exhibited cytotoxicity starting at 24 h of treatment,while it reduced Ki67 expression in the nucleus.The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells,which may be related to the activation of AhR.IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells.At low concentrations(<12.5μmol/L),IAAD only exhibited cytotoxic effects without promoting cell invasion.In addition,predictions based on online databases,protein-protein interaction analysis,and molecular docking showed that IAAD can bind to matrix metalloproteinase-9(MMP9),angiotensin converting enzyme(ACE),poly(ADP-ribose)polymerase-1(PARP1),matrix metalloproteinase-2(MMP2),and myeloperoxidase(MPO).CONCLUSION Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC;however,at high concentrations(≥25μmol/L),it can also promote epithelial-mesenchymal transition and invasion in CRC cells.IAAD activates AhR and directly binds MMP9,ACE,PARP1,MMP2,and MPO,which partly reveals why it has a bidirectional effect.

质体ACCase Trp-1999-Leu突变对小麦田菵草生长适合度的影响

为了明确质体乙酰辅酶A羧化酶(ACCase)Trp-1999-Leu突变对小麦田菵草生长适合度的影响,以ACCase基因CT区域的1999位纯合突变型(Leu/Leu, RR)和纯合野生型(Trp/Trp, SS)菵草为对象,采用温室盆栽法探究两种基因型菵草在早期生长阶段及营养生长阶段的株高及地上生物量、成熟期的繁殖力,在室内与田间不同条件下测定两种基因型菵草与小麦竞争能力的差异,以期明确在无除草剂选择压力下该位点突变对菵草生长的影响。结果表明,在菵草生长早期的10~15 d,RR型菵草的生物量和株高分别比SS型低24.9%和11.5%;在营养生长阶段,RR型菵草的相对生长速率(RGR)和净同化率(NAR)分别比SS型菵草低18.2%和28.6%,叶面积比(LAR)高于SS型14.0%,但是二者的地上生物量无显著差异。在成熟期,RR分配给生殖器官的资源更少,无论是繁殖力还是平均植株总种子重量均显著低于SS,分别低13.1%、11.4%。竞争力方面,在室内条件下,随着小麦密度的升高,RR基因型菵草地上生物量及种子产量均显著低于SS型;在田间试验中也证实了室内研究的结果,RR型与SS型菵草相比,与小麦的竞争力更弱。因此,ACCase Trp-1999-Leu基因突变会使抗性菵草产生明显的繁殖力和竞争力适合度代价,研究结果可为该基因型菵草的进化和治理提供一定的理论基础。

TRPS1、GATA3在乳腺癌中的表达及其临床意义

目的研究TRPS1、GATA3在乳腺癌中的表达及其临床意义。方法选择徐州市肿瘤医院2019年1月至2020年12月120例乳腺癌手术患者设为研究组,70例乳腺良性病变手术患者设为对照组。比较两组的GATA3、TRPS1阳性表达率,以及不同分型乳腺癌的GATA3、TRPS1阳性表达率。结果研究组的GATA3、TRPS1阳性表达率均高于对照组,差异有统计学意义(P<0.001)。120例患者中Luminal A型45例、Luminal B型34例、HER2过表达型22例、三阴型19例。Luminal A型、Luminal B型、HER2过表达型患者的GATA3阳性表达率高于三阴型患者,Luminal A型患者的GATA3阳性表达率高于HER2过表达型患者,差异均有统计学意义(P<0.05)。不同分型乳腺癌患者的TRPS1阳性表达率比较,差异均无统计学意义(P>0.05)。结论GATA3在Luminal A型和B型乳腺癌中表达率较高,TRPS1在所有分型乳腺癌中均较高表达,可辅助特殊类型乳腺癌及乳腺癌转移灶的诊断。

中医药与TRP通道相关研究现状的可视化分析

目的对中医药与瞬时受体电位(transient receptor potential,TRP)通道的国内研究进展及前沿热点进行分析,预测未来研究热点,为今后研究提供参考。方法以中国知网(CNKI)、万方以及维普数据库为资料来源,收集建库至2022年9月6日中医药与TRP通道相关的中文文献,采用文献计量学方法对符合研究标准的文献进行统计分析,并运用CiteSpace 6.1.R2及VOSviewer 1.6.16软件进行可视化。结果最终纳入文献130篇,自2007年首次发文至今,中医药与TRP通道相关的文献在经历阶段性的快速上升后,目前处于稳定趋势,其中《中国中医基础医学杂志》为发表相关文献最多的杂志。核心作者共24人,发文量最高作者为杨桢,核心研究机构8家,以北京中医药大学为代表。关键词可视化分析提示,中医药与TRP通道相关的研究,主要集中在中医药基础研究、呼吸道疾病、消化道疾病、骨关节疾病及肾病。其中慢性咳嗽、咳嗽变异性哮喘、气道高反应性、神经源性炎症、腹泻型肠易激综合征、骨质疏松、足细胞等是中医药与TRP通道相关研究的前沿热点。结论国内中医药与TRP通道结合的研究起步较晚,处于上升阶段,且尚未形成成熟而集中的研究热点,目前中医药研究与TRP通道的结合在中医药相关理论阐释、肾病及呼吸道、消化道疾病的研究较多,可能成为接下来的研究热点。

Pectin modulates intestinal immunity in a pig model via regulating the gut microbiota-derived tryptophan metabolite-AhR-IL22 pathway

Background Pectin is a heteropolysaccharide that acts as an intestinal immunomodulator,promoting intestinal development and regulating intestinal flora in the gut.However,the relevant mechanisms remain obscure.In this study,pigs were fed a corn-soybean meal-based diet supplemented with either 5%microcrystalline cellulose(MCC)or 5%pectin for 3 weeks,to investigate the metabolites and anti-inflammatory properties of the jejunum.Result The results showed that dietary pectin supplementation improved intestinal integrity(Claudin-1,Occludin)and inflammatory response[interleukin(IL)-10],and the expression of proinflammatory cytokines(IL-1β,IL-6,IL-8,TNF-α)was down-regulated in the jejunum.Moreover,pectin supplementation altered the jejunal microbiome and tryptophan-related metabolites in piglets.Pectin specifically increased the abundance of Lactococcus,Enterococcus,and the microbiota-derived metabolites(skatole(ST),3-indoleacetic acid(IAA),3-indolepropionic acid(IPA),5-hydroxyindole-3-acetic acid(HIAA),and tryptamine(Tpm)),which activated the aryl hydrocarbon receptor(AhR)pathway.AhR activation modulates IL-22 and its downstream pathways.Correlation analysis revealed the potential relationship between metabolites and intestinal morphology,intestinal gene expression,and cytokine levels.Conclusion In conclusion,these results indicated that pectin inhibits the inflammatory response by enhancing the AhR-IL22-signal transducer and activator of transcription 3 signaling pathway,which is activated through tryptophan metabolites.

T cells in pancreatic cancer stroma:Tryptophan metabolism plays an important role in immunoregulation

Several studies have shown that the immune system is highly regulated by tryptophan metabolism,which serves as an immunomodulatory factor.The indoleamine 2,3-dioxygenase 1(IDO1),as an intracellular enzyme that participates in metabolism of the essential amino acid tryptophan in the kynurenine pathway,is an independent prognostic marker for pancreatic cancer(PC).First,overexpression of IDO1 inhibits the maturation of dendritic cells and T-cell proliferation in the liver and spleen.Second,the high expression of kynurenine induces and activates the aryl hydrocarbon receptor,resulting in upregulated programmed cell death protein 1 expression.Third,the induction of IDO1 can lead to loss of the T helper 17 cell/regulatory T cell balance,mediated by the proximal tryptophan catabolite from IDO metabolism.In our study,we found that overexpression of IDO1 upregulated CD8+T cells and reduced natural killer T cells in pancreatic carcinoma in mice.Hence,it may be essential to pay more attention to tryptophan metabolism in patients,especially those who are tolerant to immunotherapy for PC.

多肽Trp-Pro_(n)-Tyr中色氨酸和酪氨酸之间的超快质子耦合电子转移

本文使用稳态吸收与荧光光谱、纳秒时间分辨荧光光谱和飞秒时间分辨瞬态吸收光谱技术,在pH=3、7和10的三种条件下,全面研究了一系列模型多肽(Trp-Pro_(n)-Tyr,WPnY,n=0、1、2、3、5)中色氨酸(Trp,W)和酪氨酸(Tyr,Y)之间的超快质子耦合电子转移特性:研究发现多肽中色氨酸的荧光猝灭程度与肽链的长度呈负相关.在WPY中,色氨酸的荧光被强烈猝灭,并且这种猝灭效应与pH值高度相关.稳态吸收光谱表明,WPY中存在与其他模型多肽明显不同的缺色性;瞬态吸收光谱也展现出其激发态衰减比其他模型多肽更快,尤其是在pH=10时,这可能归因于色氨酸和酪氨酸之间高效的质子耦合电子转移效应.由于WPY中色氨酸和酪氨酸之间的距离极短,两个氨基酸之间发生了偶极相互作用,从而实现了酪氨酸向色氨酸“直接式”的质子和电子转移过程。其他模型多肽中,两个氨基酸之间的距离较远,只能发生缓慢和长程的“间接式”质子和电子转移.此外,本文对WY和WP二肽的研究结果进一步表明,色氨酸可能与多肽的肽骨架或脯氨酸之间还存在更复杂的相互作用:该研究为色氨酸-酪氨酸“二联体”中的电子和质子转移机制提供了实验证据,可以帮助人们了解蛋白质中色氨酸自由基的清除机制,也为进一步研究蛋白质的抗氧化自我保护功能提供了指导意义。

Ochratoxin A induces abnormal tryptophan metabolism in the intestine and liver to activate AMPK signaling pathway

Background Ochratoxin A(OTA)is a mycotoxin widely present in raw food and feed materials and is mainly pro-duced by Aspergillus ochraceus and Penicillium verrucosum.Our previous study showed that OTA principally induces liver inflammation by causing intestinal flora disorder,especially Bacteroides plebeius(B.plebeius)overgrowth.However,whether OTA or B.plebeius alteration leads to abnormal tryptophan-related metabolism in the intestine and liver is largely unknown.This study aimed to elucidate the metabolic changes in the intestine and liver induced by OTA and the tryptophan-related metabolic pathway in the liver.Materials and methods A total of 30 healthy 1-day-old male Cherry Valley ducks were randomly divided into 2 groups.The control group was given 0.1 mol/L NaHCO3 solution,and the OTA group was given 235μg/kg body weight OTA for 14 consecutive days.Tryptophan metabolites were determined by intestinal chyme metabolomics and liver tryptophan-targeted metabolomics.AMPK-related signaling pathway factors were analyzed by Western blot-ting and mRNA expression.Results Metabolomic analysis of the intestinal chyme showed that OTA treatment resulted in a decrease in intesti-nal nicotinuric acid levels,the downstream product of tryptophan metabolism,which were significantly negatively correlated with B.plebeius abundance.In contrast,OTA induced a significant increase in indole-3-acetamide levels,which were positively correlated with B.plebeius abundance.Simultaneously,OTA decreased the levels of ATP,NAD+and dipeptidase in the liver.Liver tryptophan metabolomics analysis showed that OTA inhibited the kynurenine metabolic pathway and reduced the levels of kynurenine,anthranilic acid and nicotinic acid.Moreover,OTA increased the phosphorylation of AMPK protein and decreased the phosphorylation of mTOR protein.Conclusion OTA decreased the level of nicotinuric acid in the intestinal tract,which was negatively correlated with B.plebeius abundance.The abnormal metabolism of tryptophan led to a deficiency of NAD+and ATP in the liver,which in turn activated the AMPK signaling pathway.Our results provide new insights into the toxic mechanism of OTA,and tryptophan metabolism might be a target for prevention and treatment.

Tryptophan Metabolism and Gut Microbiota

Background: Tryptophan metabolites such as serotonin, kynurenine, or kynurenic acids are considered to be the most important metabolites of gut microbiota. We wanted to know about changes in tryptophan metabolites in various diseases in which the etiology gut microbiota are considered to participate. Methods: Ultra-high speed liquid chromatography/mass spectroscopy (LC/MS) has been used to analyze simultaneously all the tryptophan metabolites, which we have explored for the first time in the world. Results: We analyzed plasma levels of tryptophan metabolites in patients with depression, autism, diabetes mellitus ‘DM’), and acute coronary syndrome (ACS). Of all the metabolites serotonin and kynurenine levels of these patients were higher than those of controls. Conclusion: Measurements of tryptophan metabolites in plasma of various diseases are important to know roles of gut microbiota in etiology, further therapeutic measures.

GPCR-TRP通道轴在瘙痒中的研究进展

瘙痒神经通路的感觉神经元分布有受体和离子通道,使它们能接受各种刺激并做出反应。G蛋白偶联受体(GPCR)是一类主要的感觉蛋白,是瘙痒通路中的主要治疗靶点。GPCR具有复杂的信号机制,来自GPCR超家族的信号汇聚到瞬时受体电位通道家族(TRPs),导致通道敏化和激活,从而放大瘙痒和神经炎症。总结和讨论GPCR-TRP通道轴的作用途径和信号机制,有助于研发更多具有选择性和针对性的治疗方法,以治疗瘙痒和神经传导通路的失调。

三肽D-Trp-Arg-Leu-NH2抑制B16黑色素瘤细胞黑色素合成的机制

为了研究三肽D-Trp-Arg-Leu-NH2(dWRL)对小鼠B16细胞的酪氨酸酶(TYR)活性、黑色素合成及相关基因和蛋白表达的影响,探讨dWRL抑制黑色素生成的可能机制,我们体外培养小鼠B16细胞,采用MTT法测定细胞增殖情况、L-多巴氧化法测定TYR活性、氢氧化钠裂解法测定细胞黑色素含量、qRT-PCR和Western Blot法分别检测药物作用后B16细胞中小眼畸形相关转录因子(MITF)、TYR的mRNA和蛋白表达水平。结果显示三肽dWRL在试验浓度范围内可明显抑制α-黑色素细胞刺激素(α-MSH)诱导的B16细胞内TYR活性、黑色素合成量及MITF、TYR基因及蛋白的表达量,且呈浓度依赖性。所以三肽dWRL在体外能抑制B16细胞黑色素的合成,上述变化可能是通过下调MITF和TYR的基因转录和蛋白表达作用来完成。

N-乙酰半胱氨酸对支气管哮喘大鼠CXCL8-CXCR1/2及TRPV1神经元敏感性的影响

目的探究N-乙酰半胱氨酸对支气管哮喘大鼠CXC趋化因子配体(CXCL)8-CXC趋化因子受体(CXCR)1/2及瞬时受体电位通道蛋白(TRP)V1神经元敏感性的影响。方法选取80只SPF级SD雄性大鼠,随机分为正常(NO)组、模型(MO)组、N-乙酰半胱氨酸(NAC)组、急支糖浆(ES)组,每组20只,对MO组、NAC组、ES组进行支气管哮喘建模,建模成功后,NAC组、ES组每天分别于腹腔内注射2 ml N-乙酰半胱氨酸注射液、急支糖浆灌胃10 g/kg剂量,NO组、MO组同期灌胃同体积生理盐水,通过苏木素-伊红(HE)染色法检测肺组织病理形态、酶联免疫吸附试验(ELISA)、实时荧光定量聚合酶链反应(RT-PCR)、Western印迹检测血清及肺组织中CXCL8、CXCR1、CXCR2、TRPV1含量、mRNA及蛋白表达,并分析N-乙酰半胱氨酸对支气管哮喘大鼠CXCL8-CXCR1/2及TRPV1神经元敏感性。结果与NO组相比,MO组咳嗽次数明显增加(P<0.05),而NAC组、ES组与MO组相比,其咳嗽次数明显降低(P<0.05),且NAC组比ES组降低明显(P<0.05);与NO组相比,MO组细支气管管腔、肺泡腔内可见渗出液、脱落的上皮细胞等,远端肺泡可见局部肺不张及周围肺大泡,且肺间质明显增厚,炎性细胞浸润明显,而与MO组比较,ES组、NAC组症状明显减少,部分肺间质的组织结构趋向正常,部分肺泡轻度扩张,且NAC组比ES组明显降低(P<0.05);与NO组对比,MO组CXCL8、CXCR1、CXCR2、TRPV1含量、mRNA及蛋白表达均明显升高(P<0.05),NAC组、ES组与MO组相比均显著降低(P<0.05),且NAC组比ES组明显降低(P<0.05)。结论N-乙酰半胱氨酸可以显著降低咳嗽次数,减少支气管哮喘症状,可使CXCL8-CXCR1/2及TRPV1神经元敏感性显著降低。

TRP通道与遗传性疾病

瞬时受体电位(TRP)通道属于一个大而多样的整合蛋白家族,作为热、化学和机械刺激的细胞传感器出现,并且是Ca2+信号的主要贡献者,在多种生理和病理过程中发挥重要作用。TRP通道与许多疾病有关,包括了众多编码TRP通道的基因缺陷引起的遗传性疾病(TRP通道病)。本文主要对TRP通道与相应遗传性疾病进行综述。

Kynurenine pathway of tryptophan metabolism in pathophysiology and therapy of major depressive disorder

Serotonin deficiency in major depressive disorder(MDD)has formed the basis of antidepressant drug development and was originally attributed to induction of the major tryptophan(Trp)-degrading enzyme,liver Trp 2,3-dioxygenase(TDO),by cortisol,leading to decreased Trp availability to the brain for serotonin synthesis.Subsequently,the serotonin deficiency was proposed to involve induction of the extrahepatic Trp-degrading enzyme indoleamine 2,3-dioxygenase(IDO)by proinflammatory cytokines,with inflammation being the underlying cause.Recent evidence,however,challenges this latter concept,as not all MDD patients are immune-activated and,when present,inflammation is mild and/or transient.A wide range of antidepressant drugs inhibit the activity of liver TDO and bind specifically to the enzyme,but not to IDO.IDO induction is not a major event in MDD,but,when it occurs,its metabolic consequences may be masked and overridden by upregulation of kynurenine monooxygenase(KMO),the gateway to production of modulators of immune and neuronal functions.KMO appears to be activated in MDD by certain proinflammatory cytokines and antidepressants with anti-inflammatory properties may block this activation.We demonstrate the ability of the antidepressant ketamine to dock(bind)to KMO.The pathophysiology of MDD may be underpinned by both the serotonin deficiency and glutamatergic activation mediated respectively by TDO induction and N-methyl-D-aspartate receptor activation.Inhibition of TDO and KMO should be the focus of MDD pharmacotherapy.

5G网络基于UDT信令跟踪的TRP覆盖问题识别方法研究

传统的4G优化方法难以发现Hyper cell小区内存在的弱覆盖、越区覆盖、乒乓切换、重叠覆盖等相关问题,NR网络中提出了TRP传输和接收节点概念,将多个TRP合并成一个逻辑小区并称之为合并小区Hyper cell,本研究通过引入基于UDT信令跟踪的TRP问题识别方法,对5G Hyper cell内的TRP覆盖问题进行分析研究,能够准确有效地发现小区内TRP间存在的问题,开展针对性优化,提升网络质量及业务体验,为5G网络优化提供强有力的问题识别手段。