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.

高效液相色谱法测定孕妇血清中色氨酸及其代谢产物Kynurenine

[目的]建立一种高效液相色谱法测定孕妇血清中的色氨酸（Tyrptophan）及其代谢产物Kynurenine的方法。[方法]反相高效液相色谱法。外标法，ZORBAX Extend-C18柱，4．6mmID×250mm，流动相为甲醇：0．001mol／L磷酸二氢钾（采用PH=4）（12：88），流速1．3ml／min，检测波长245nm。[结果]色氨酸线性范围2．56～307．06μmol／L，r=0．9999；Kynurenine线性范围0．12～5．05μmol／L，r=0．9997。30例孕妇血清色氨酸为49．73±7．48μmol／L，其代谢产物KN为：0．74±0．33μmol／L。[结论]本法简便，准确，适用于临床和科研。

Helicobacter pylori and serum kynurenine-tryptophan ratio in patients with colorectal cancer

AIM: To evaluate how Helicobacter pylori(H. pylori) is able to evade the immune response and whether it enhances systemic immune tolerance against colorectal cancer.METHODS: This prospective randomized study involved 97 consecutive colorectal cancer patients and 108 cancer-free patients with extra-digestive diseases. Colorectal cancer and cancer-free patients were assigned into subgroups according to H. pylori Ig G seropositivity. Exposure to H. pylori was determined by Ig G seropositivity which was detected by enzyme linked immunoassay(ELISA). Serum neopterin levels were measured by ELISA. Serum tryptophan, kynurenine, and urinary biopterin concentrations were measured by high performance liquid chromatography. Serum nitrite levels were detected spectrophotometrically. Serum indoleamine 2,3-dioxygenase activity was estimated by the kynurenine to tryptophan ratio and by assessing the correlation between serum neopterin concentrations and the kynurenine to tryptophan ratio. The frequencies of increased serum kynurenine to tryptophan ratio of H. pylori seronegative and seropositive colorectal cancer subgroups were estimated by comparing them with the average kynurenine to tryptophan ratio of H. pylori seronegative tumor-free patients.RESULTS: Compared with respective controls, in both H. pylori seronegative and seropositive colorectal cancer patients, while serum tryptophan levels were decreased(controls vs patients; seronegative: 20.37 ± 0.89 μmol/L vs 15.71 ± 1.16 μmol/L, P < 0.05; seropositive: 20.71 ± 0.81 μmol/L vs 14.97 ± 0.79 μmol/L, P < 0.01) the kynurenine to tryptophan ratio was significantly increased(controls vs patients; seronegative: 52.85± 11.85 μmol/mmol vs 78.91 ± 8.68 μmol/mmol, P < 0.01, seropositive: 47.31 ± 5.93 μmol/mmol vs 109.65 ± 11.50 μmol/mmol, P < 0.01). Neopterin concentrations in cancer patients were significantly elevated compared with controls(P < 0.05). There was a significant correlation between serum neopterin levels and kynurenine/tryptophan in control and colorectal cancer patients groups(r s = 0.494, P = 0.0001 and r s= 0.293, P = 0.004, respectively). Serum nitrite levels of H. pylori seropositive cancer cases were significantly decreased compared with seropositive controls(controls vs patients; 26.04 ± 2.39 μmol/L vs 20.41 ± 1.48 μmol/L, P < 0.05) The decrease in the nitrite levels of H. pylori seropositive cancer patients may be attributed to excessive formation of peroxynitrite and other reactive nitrogen species.CONCLUSION: A significantly high kynurenine/tryptophan suggested that H. pylori may support the immune tolerance leading to cancer development, even without an apparent upper gastrointestinal tract disease.

Inhibiting the kynurenine pathway in spinal cord injury: multiple therapeutic potentials?

Chronic induction of the kynurenine pathway（KP） contributes to neuroinflammation by producing the excitotoxin quinolinic acid（QUIN）. This has led to significant interest in the development of inhibitors of this pathway, particularly in the context of neurodegenerative disease. However, acute spinal cord injury（SCI） also results in deleterious increases in QUIN, as secondary inflammatory processes mediated largely by infiltrating macrophages, become predominant. QUIN mediates significant neurotoxicity primarily by excitotoxic stimulation of the N-methyl-D-aspartate receptor, but other mechanisms of QUIN toxicity are known. More recent focus has assessed the contribution that neuroinflammation and modulations in the KP make in mood and psychiatric disorders with recent studies linking inflammation and modulations in the KP, to impaired cognitive performance and depressed mood in SCI patients. We hypothesize that these findings suggest that in SCI, inhibition of QUIN production and other metabolites, may have multiple therapeutic modalities and further studies investigating this are warranted. However, for central nervous system-based conditions, achieving good blood-brain-barrier permeability continues to be a limitation of current KP inhibitors.

Kynurenine plays an immunosuppressive role in 2,4,6-trinitrobenzene sulfate-induced colitis in mice

BACKGROUND Inflammatory bowel disease,such as Crohn’s disease and ulcerative colitis,is characterized by chronic intestinal inflammation leading to intestinal mucosal damage.Inflammatory bowel disease causes dysregulation of mucosal T cell responses,especially the responses of CD4+T cells.Previously,we demonstrated that indoleamine-2,3-dioxygenase plays an immunosuppressive role in 2,4,6-trinitrobenzene sulfate(TNBS)-induced colitis.Although indoleamine-2,3-dioxygenase exerts immunosuppressive effects by altering the local concentration of tryptophan(Trp)and immunomodulatory Trp metabolites,the specific changes in immune regulation during colitis caused by Trp metabolites and its related enzymes remain unclear.AIM To investigate role of kynurenine 3-monooxygenase(KMO)in TNBS-induced colitis and involvement of Trp metabolites in maintenance of intestinal homeostasis.METHODS Colitis was induced in eight-week-old male KMO+/+or KMO−/−mice of C57BL/6N background using TNBS.Three days later,the colon was used for hematoxylin-eosin staining for histological grading,immunohistochemical or immunofluorescence staining for KMO,cytokines,and immune cells.Inflammatory and anti-inflammatory cytokines were measured using quantitative RT-PCR,and kynurenine(Kyn)pathway metabolites were measured by high-performance liquid chromatography.The cell proportions of colonic lamina propria and mesenteric lymph nodes were analyzed by flow cytometry.RESULTS KMO expression levels in the colonic mononuclear phagocytes,including dendritic cells and macrophages increased upon TNBS induction.Notably,KMO deficiency reduced TNBS-induced colitis,resulting in an increased frequency of Foxp3+regulatory T cells and increased mRNA and protein levels of antiinflammatory cytokines,including transforming growth factor-βand interleukin-10.CONCLUSION Absence of KMO reduced TNBS-induced colitis via generation of Foxp3+regulatory T cells by producing Kyn.Thus,Kyn may play a therapeutic role in colon protection during colitis.

Kynurenine pathway metabolism and neuroinflammatory disease

Immune-mediated activation of tryptophan（TRYP） catabolism via the kynurenine pathway（KP） is a consistent finding in all inflammatory disorders.Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites,including quinolinic acid（QUIN） in neuroinflammatory neurological disorders,including Alzheimer＇s disease（AD）,multiple sclerosis,amylotropic lateral sclerosis（ALS）,and AIDS related dementia complex（ADC）.Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response.Under physiological conditions,QUIN is metabolized to the essential pyridine nucleotide,nicotinamide adenine dinucleotide（NAD＋）,which represents an important metabolic cofactor and electron transporter.NAD＋ also serves as a substrate for the DNA ‘nick sensor＇ and putative nuclear repair enzyme,poly（ADP-ribose） polymerase（PARP）.Free radical initiated DNA damage,PARP activation and NAD＋ depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease.

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。

Differences of Plasma Levels of Tryptophan, Serotonin, 5-Hydroxyindole Acetic Acid, and Kynurenine between Healthy People and Patients of Major Monopolar Depression at Various Age and Gender

Background: It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of major monopolar depression (MMD). Methods: Ultra high-speed liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive patients. Results: There are no significant differences between plasma levels of TRP between HC and MMD. Plasma levels of TRP of HC are higher in young men, young women, old men, and old women in this order. Serotonin (5-HT) levels are higher in MMD than HC. Plasma levels of 5-HIAA of HC are also higher than those of patients of MMD. Plasma levels of kynurenine (KYN) of healthy old men and old women are higher than those of young men and old women. Plasma levels of KYN are higher in old women and young men of MMD than those of HC. Conclusion: Plasma levels of 5-HT are higher in patients of MMD than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation may increase plasma levels of 5-HT in MMD.

Research progress of kynurenine pathway in Alzheimer's disease

The kynurenine pathway(KP)has been shown to be involved in the pathophysiology of dementia diseases.Among the dementia diseases,the neurodegenerative diseases Alzheimer's disease and cerebrovascular diseases are vascular.The highest incidence of dementia.KP activation results in the production of neuroactive metabolites,which may interfere with normal neuronal function,leading to the appearance of symptoms of cognitive impairment.This review investigated KP's involvement in the neurological diseases Alzheimer's disease and vascular dementia,suggesting that KP is a potential therapeutic target for both diseases.

Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec-15 axis in immune escape

Background:Metabolic reprograming and immune escape are two hallmarksof cancer.However,how metabolic disorders drive immune escape in head andneck squamous cell carcinoma(HNSCC)remains unclear.Therefore,the aim ofthe present study was to investigate the metabolic landscape of HNSCC and itsmechanism of driving immune escape.Methods:Analysis of paired tumor tissues and adjacent normal tissues from69 HNSCC patients was performed using liquid/gas chromatography-mass spectrometry and RNA-sequencing.The tumor-promoting function of kynurenine(Kyn)was explored in vitro and in vivo.The downstream target of Kyn wasinvestigated in CD8^(+)T cells.The regulation of CD8+T cells was investigatedafter Siglec-15 overexpression in vivo.An engineering nanoparticle was establishedto deliver Siglec-15 small interfering RNA(siS15),and its association withimmunotherapy response were investigated.The association between Siglec-15and CD8^(+)programmed cell death 1(PD-1)^(+)T cells was analyzed in a HNSCCpatient cohort.Results:A total of 178 metabolites showed significant dysregulation in HNSCC,including carbohydrates,lipids and lipid-like molecules,and amino acids.Among these,amino acid metabolism was the most significantly altered,especiallyKyn,which promoted tumor proliferation and metastasis.In addition,most immune checkpoint molecules were upregulated in Kyn-high patientsbased on RNA-sequencing.Furthermore,tumor-derived Kyn was transferredinto CD8^(+)T cells and induced T cell functional exhaustion,and blockingKyn transporters restored its killing activity.Accroding to the results,mechanistically,Kyn transcriptionally regulated the expression of Siglec-15 via arylhydrocarbon receptor(AhR),and overexpression of Siglec-15 promoted immuneescape by suppressing T cell infiltration and activation.Targeting AhR in vivoreduced Kyn-mediated Siglec-15 expression and promoted intratumoral CD8^(+)Tcell infiltration and killing capacity.Finally,a NH_(2)-modified mesoporous silicananoparticle was designed to deliver siS15,which restored CD8^(+)T cell functionstatus and enhanced anti-PD-1 efficacy in tumor-bearing immunocompetentmice.Clinically,Siglec-15 was positively correlated with AhR expression andCD8+PD-1^(+)T cell infiltration in HNSCC tissues.Conclusions:The findings describe the metabolic landscape of HNSCC comprehensivelyand reveal that the Kyn/Siglec-15 axis may be a novel potentialimmunometabolism mechanism,providing a promising therapeutic strategy forcancers.

KYN系列12 kV开关柜真空断路器灭弧室触头温度间接测算

断路器在各电压等级电网中担负关合、承载正常电气回路及各类故障电流的重要作用,其灭弧室触头温度作为重要的性能参数直接影响开断和负载能力,一直是设备运行状态在线检测的热点和难点。为解决KYN系列开关柜真空断路器灭弧室触头温度无法直接监测的问题,以用于KYN28A–12/T3150–40型开关柜的HYD–12/3150–40型固封极柱为实际研究对象,通过建立仿真分析模型,利用ANSYS仿真软件对该模型进行电磁–温度多物理场耦合分析。首先,通过比较1.1倍额定电流下的模型温度仿真结果与现场实际温升试验的相同部位温度来验证仿真模型的准确性;然后,对KYN系列开关柜真空断路器灭弧室触头温度的影响因素进行研究;最后,基于偏最小二乘回归法,提出通过测量环境温度、负荷电流、上触臂温度来实现触头温度的间接测算方法,结果表明触头温度仿真结果与算法计算结果几乎相等。该研究内容可为处于稳定工作状态下的KYN系列开关柜中的真空断路器灭弧室触头温度特性研究及其在线监测提供方法和理论支撑。

KYN□-40.5型铠装移开式交流金属封闭开关设备绝缘件的选择与应用

阐述了KYN□-40.5型铠装移开式交流金属封闭开关设备在性能方面上绝缘件选择的重要性。首先,针对穿墙套管和触头盒的设计进行分析,提出了具有屏蔽设计的穿墙套管与触头盒的设计方案,提高绝缘件的寿命;其次,通过对绝缘件的局部放电参数进行监控,实现对绝缘件的质量把控;最后,针对绝缘件会出现的凝露现象,提出了不同场景下的防凝露方案,保证开关设备绝缘性能。着重分析了40.5 kV绝缘件的性能指标、制作工艺、质量把控手段以及开关设备的方案设计等方面的内容,为绝缘件性能的提高提供了有力的保证。

KYN高压柜操作中存在的问题及改进措施

目前KYN型高压开关柜是高压成套设备中的主流柜型,该开关设备中的联锁功能对防止高压柜误操作具有很好的保障作用。文章在KYN型高压柜开关设备联锁设计的基础上,对高压柜日常操作中的接地刀闸的验电操作、试验操作中的二次插头等问题进行了分析,并提出了相应的改进措施,期望可以更好地提升高压柜的操作安全性。

犬尿氨酸通路在儿童神经发育障碍性疾病中的研究进展

色氨酸在体内主要通过犬尿氨酸通路(KP)代谢为血清素、褪黑素和烟酰胺腺嘌呤二核苷酸等生物活性物质,与多种器官和细胞的生理功能密切相关。KP中重要酶活性和代谢物水平的改变通过影响受体和调节细胞信号传导的方式影响儿童脑发育。该研究主要围绕KP及其代谢产物在儿童神经发育中的作用进行综述,希望为儿童神经发育障碍性疾病的协助诊断和治疗干预提供新的切入点。

背俞功能带推法对慢性疲劳综合征大鼠肠道菌群及色氨酸代谢的影响

目的探究背俞功能带推法改善慢性疲劳综合征(chronic fatigue syndrome,CFS)大鼠的症状,以及对其肠道菌群和色氨酸代谢的影响。方法选取SPF级SD大鼠24只,随机分为空白组8只、造模组16只,造模组制备CFS模型21 d,模型制备成功后随机分为模型组和推法组,每组8只。推法干预14 d,做旷场实验及力竭游泳实验等行为学实验后,取大鼠血清、结肠进行酶联免疫吸附法检测血清色氨酸(tryptophan,TRP)、犬尿氨酸(kynurenine,KYN)及结肠吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO),取肠道粪便进行16 s rRNA测序分析肠道菌群结构及多样性。结果与空白组大鼠相比,模型组大鼠总路程、跨格数、中心区时间和路程、进入中心区次数力竭游泳时间均显著减少(P<0.01);与模型组相比,推法组大鼠上述各项指标均增加(P<0.05)。在门水平,与空白组相比,模型组厚壁菌门、拟杆菌门和疣微菌门比例下降,变形菌门和酸杆菌门比例明显上升;与模型组相比,推法组厚壁菌门和酸杆菌门比例下降,而拟杆菌门和变形菌门比例升高。在属水平上,与空白组相比,模型组中罗姆布茨菌属(Romboutsia)和疣微菌科UCG-005菌属(Ruminococcaceae_UCG-005,简称UCG-005)的比例明显降低,而乳杆菌属(Lactobacillus)和双歧杆菌属(Bifidobacterium)比例明显增加;与模型组相比,推法组Lactobacillus和杜氏杆菌属(Dubosiella)比例下降,而Romboutsia和UCG-005比例上升。Alpha和Beta多样性分析,与空白组相比,模型组的菌群丰富度和多样性均降低;与模型组相比,推法组大鼠菌群丰富度和多样性有明显上升;但组间差异均无统计学意义(P>0.05)。LEfSe分析中,与空白组相比,模型组的优势物种主要聚集在目、科、属,推法组的优势物种主要聚集在科、属。与空白组大鼠相比,模型组大鼠血清TRP含量显著降低(P<0.01),血清KYN和结肠IDO含量明显升高(P<0.01);与模型组相比,推法组大鼠血清TRP含量明显升高(P<0.01),血清KYN和结肠IDO含量降低(P<0.05)。相关性分析发现,与TRP相关性较大的菌属包括Lachnospiraceae_NK4A136_group、Lactobacillus、Romboutsia等(P<0.05),与KYN相关性较大的菌属包括Bifidobacterium05、Lachnospiraceae_NK4A136_group、UCG-005(P<0.05或P<0.01),与IDO相关性较大的菌属包括Allobaculum、Lachnospiraceae_NK4A136_group、Romboutsia(P<0.05或P<0.01)。结论背俞功能带推法能明显改善CFS大鼠的疲劳以及焦虑症状,调节菌群代谢物TRP、KYN及结肠IDO含量,对肠道菌群结构及其多样性有一定的调节作用,且部分菌属与TRP、KYN、IDO具有相关性。

KYN28A-12型中置式开关柜标准化设计研究

为满足不同厂家设备在一定范围和一定时期的通用互换使用,提升开关柜设备的运维便利性,选择目前市场上应用较多且运行相对成熟可靠的KYN28A-12型中置式开关柜开展标准化设计研究,介绍了标准化设计的目的、设计思路、输入条件和主要设计内容。重点分析了KYN28A-12型中置式开关柜的典型方案确定,对一次接口及土建接口、二次接口以及关键元件的标准化设计原则及结果进行了详细说明,在满足配网设备需求的基础上兼顾变电站中配电设备的要求,提出了统一的标准化设计方案,为后续标准化建设工作提供重要支撑。

液相色谱串联质谱法测定青少年抑郁症患者血清和尿液中色氨酸代谢物的水平

目的观察并比较液相色谱串联质谱技术检测青少年抑郁症患者血清和尿液中色氨酸-犬尿氨酸(TRP-KP)通路代谢物的浓度。方法对该通路中主要代谢物如色氨酸(TRP)、犬尿氨酸(KYN)、犬尿酸(KYNA)和3-羟基犬尿氨酸(3-HK)采用同位素标记法进行定量分析。使用岛津C18色谱柱,0.2%甲酸水溶液和乙腈进行梯度洗脱分离,7 min内采用正离子和多反应监测模式进行检测。考察线性范围、精密度等参数。用该方法检测143例青少年抑郁症患者和110例体检健康者血液和尿液样本并比较。结果以TRP为例,血清和尿液的线性范围分别为0.54~107.84μmol/L和0.74~147.06μmol/L。批内变异系数(CV)≤6.3%,批间CV≤3.22%,实验室总CV≤6.5%。抑郁组和对照组血清和尿液检测结果表明,抑郁组KYNA、KYN和TRP水平低于对照组,而3-HK水平高于对照组,差异具有统计学意义(P<0.01)。除TRP外,其他代谢物水平在尿液中显著高于血清中,差异具有统计学意义(P<0.01)。结论与血清相比,尿液中TRP-KP的代谢物即KYN、KYNA和3-HK浓度更高,由于尿液收集过程是无创的,因此检测尿液中TRP-KP代谢物具有更大的优势。

血清IDO和KYN在溃疡性结肠炎中的临床价值研究

目的检测吲哚胺2,3-双加氧酶(IDO)和犬尿氨酸(KYN)在溃疡性结肠炎(UC)患者中的表达水平,利用受试者工作特征(ROC)曲线分析血清IDO、KYN诊断活动期UC的价值。方法 60例UC组、18例疾病对照组和20例健康对照组。采用免疫组化法检测UC组结肠黏膜中IDO的表达,ELISA法检测3组血清中IDO、KYN和C反应蛋白(CRP)水平,利用ROC曲线进行分析。结果①UC组血清中IDO和KYN水平与结肠黏膜IDO表达量呈正相关(P<0.05);②UC组患者血清IDO及KYN水平高于疾病对照组和健康对照组(P<0.05);③UC组中,活动期患者血清IDO、KYN水平高于缓解期(P<0.01),并随炎症严重程度升高而升高;④活动期UC组IDO、KYN水平与疾病活动度、CRP水平呈正相关;⑤IDO、KYN、CRP的ROC曲线下面积分别为0.976、0.856和0.864;最佳截断值分别为53.66 U/L、2.34 nmol/L和1.75 mg/ml;灵敏度分别为90.5%、78.65%和100.0%;特异度分别为94.4%、83.3%和61.1%;Youden指数分别为0.849 2、0.619 0和0.611 1。结论UC患者血清IDO和KYN水平可以作为判断UC患者炎症程度的重要指标,血清IDO、KYN和CRP水平对活动期UC有重要的诊断价值,其中IDO诊断价值高于KYN和CRP。

禾谷镰孢犬尿氨酸途径关键酶基因的鉴定与表达分析

为了鉴定禾谷镰孢中KP关键酶基因及其功能,本研究采用生物信息学方法对禾谷镰孢的KP关键酶基因进行了系统分析。研究发现,禾谷镰孢含有KP关键酶IDO(吲哚-2,3-双加氧酶)、AFMID(芳基甲酰胺酶)、KAT(犬尿氨酸氨基转移酶)、KMO(犬尿氨酸单加氧酶)、KYN(犬尿氨酸酶)和HAO(羟基酸氧化酶)。通过分析禾谷镰孢的表达谱数据,发现KP关键酶基因FgIDO、FgAFMID、FgKAT、FgKMO、FgKYN和FgHAO在分生孢子发育、菌丝生长和侵染玉米茎秆的不同阶段表现出较高的表达水平,表明这些基因可能参与分生孢子发育、菌丝生长和侵染过程。整合研究结果和现有文献信息,绘制了禾谷镰孢KP及其关键酶催化反应的模式图,为阐明禾谷镰孢KP调控病菌生长发育和致病力的功能与机制奠定了基础。

培元解郁方对慢性应激BALB/c小鼠的抗抑郁作用及TRY-KYN代谢途径的调节

目的:研究四逆散、天丝饮、培元解郁方的抗抑郁作用及其对血清皮质酮含量和色氨酸(TRP)-犬尿氨酸(KYN)途径关键代谢酶色氨酸2,3-双加氧酶(TDO)的影响。方法:使用束缚加噪声造成小鼠抑郁模型,采用Noldus Etho Vision XT9系统采集分析小鼠强迫游泳不动时间,采用HPLC-MS/MS技术检测血清色氨酸(TRP)、犬尿氨酸(KYN)、犬尿烯酸(KA)、喹啉酸(Q)、皮质酮(C)含量,实时荧光定量PCR检测肝组织中TDO的mRNA表达水平。结果:束缚加噪声应激5d后可以引起模型组小鼠强迫游泳不动时间延长,血清皮质酮含量增高,KYN/TRP、KYN/KA比值升高,KYN/Q比值降低。四逆散、天丝饮、培元解郁方能缩短小鼠不动时间(P<0.01),降低血清皮质酮含量(P<0.05),提高KYN/TRP、KYN/Q比值(P<0.05),降低KYN/KA比值。结论:四逆散、天丝饮、培元解郁方具有抗抑郁药物样作用,这一作用与对抗应激引发的血清皮质酮升高,抑制色氨酸-犬尿氨酸代谢途径中的神经毒性代谢产物产生并提高神经保护作用有关。