photophobia

畏光
  • 文章类型: Journal Article
    背景:前庭性偏头痛(VM)是一种以发作性眩晕为特征的常见前庭疾病。然而,在VM中,畏光与视觉触发因素之间的关系仍有待探索.我们调查了VM发作期间畏光与VM患者发作间光敏性和视觉触发头晕的相关性。
    方法:我们招募了诊断为VM的患者,有或没有畏光,在中国的七个专门的眩晕和头痛诊所。还包括健康个体作为对照组。使用横断面调查设计,我们收集了与闪烁触发的光强和头晕频率有关的数据,眩光,眩光使用头痛触发敏感性和避免性问卷和眼睛疲劳。
    结果:共招募了366名患者。由闪烁引起的头晕的光敏性和频率,眩光,眩光与没有畏光的患者和对照组参与者相比,在有VM和畏光的患者中观察到的眼睛疲劳显着升高(P<0.001)。光敏感性水平与闪烁引起的头晕频率之间存在显着正相关,眩光,眩光VM和畏光患者的眼睛疲劳(P<0.001)。
    结论:本研究明确确立了畏光与发作间光敏性和视觉触发性头晕的正相关,强烈主张需要进一步研究基于暴露的治疗来管理VM。
    背景:ClinicalTrial.gov标识符,NCT04939922,回顾性注册,2021年6月14日。
    BACKGROUND: Vestibular migraine (VM) is a prevalent vestibular disorder characterized by episodic vertigo. However, the relationship between photophobia and visual triggers in VM remains unexplored. We investigated the correlation of photophobia during the VM attack with interictal photosensitivity and visually triggering dizziness in patients with VM.
    METHODS: We enrolled patients diagnosed with VM, with or without photophobia, across seven specialized vertigo and headache clinics in China. Healthy individuals were also included as a control group. Using a cross-sectional survey design, we collected data related to light intensity and dizziness frequency triggered by flicker, glare, and eyestrain using the Headache Triggers Sensitivity and Avoidance Questionnaire.
    RESULTS: A total of 366 patients were recruited. The photosensitivity and frequency of dizziness induced by flicker, glare, and eyestrain observed in patients with VM and photophobia were significantly elevated compared with those in patients without photophobia and control participants (P < 0.001). A significant positive correlation was observed between photosensitivity levels and dizziness frequency triggered by flicker, glare, and eyestrain in patients with VM and photophobia (P < 0.001).
    CONCLUSIONS: This study unequivocally established a positive association of ictal photophobia with interictal photosensitivity and visually triggering dizziness, strongly advocating the need for further research on exposure-based therapies for managing VM.
    BACKGROUND: ClinicalTrial.gov Identifier, NCT04939922, retrospectively registered, 14th June 2021.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:偏头痛是一种常见的原发性头痛,先前的研究强调了氧化应激和炎症途径在其发病机理和慢性中的重要作用。现有证据表明D1-3-正丁基苯酞(NBP)减轻氧化应激和炎症的能力,从而在许多中枢神经系统疾病中赋予神经保护益处。然而,NBP在偏头痛中的具体治疗意义仍有待阐明.
    方法:我们通过反复腹腔注射硝酸甘油(NTG,10mg/kg),预防性治疗通过给予NBP(30mg/kg,60mg/kg,在每次NTG注射之前通过管饲法120mg/kg)。使用vonFrey纤维评估机械阈值,使用亮/暗箱和高架迷宫评估畏光和焦虑行为。c-Fos的表达,降钙素基因相关肽(CGRP),采用免疫印迹法(WB)或免疫荧光法(IF)检测脊髓三叉神经尾核(SP5C)中的核因子红细胞2相关因子2(Nrf2)和相关通路蛋白。IL-1β的表达,IL-6,TNF-α,ELISA法检测血浆中SP5C和CGRP中的超氧化物歧化酶(SOD)和丙二醛(MDA)。使用活性氧(ROS)探针检测SP5C中ROS的表达。
    结果:在建模期结束时,慢性偏头痛小鼠表现出显著降低的机械伤害感受阈值,以及恐惧和焦虑的行为。用NBP预处理减轻伤害性敏感,畏光,和模型小鼠的焦虑,c-Fos和CGRP在SP5C和激活的Nrf2及其下游蛋白HO-1和NQO-1中的表达水平降低。通过测量相关的细胞因子,我们还发现NBP降低了氧化应激和炎症水平.最重要的是,在施用ML385抑制Nrf2后,NBP的治疗效果显著降低。
    结论:我们的数据表明,NBP可能通过激活Nrf2通路来减轻偏头痛小鼠模型的氧化应激和炎症,证实它可能是治疗偏头痛的潜在药物。
    BACKGROUND: Migraine stands as a prevalent primary headache disorder, with prior research highlighting the significant involvement of oxidative stress and inflammatory pathways in its pathogenesis and chronicity. Existing evidence indicates the capacity of Dl-3-n-butylphthalide (NBP) to mitigate oxidative stress and inflammation, thereby conferring neuroprotective benefits in many central nervous system diseases. However, the specific therapeutic implications of NBP in the context of migraine remain to be elucidated.
    METHODS: We established a C57BL/6 mouse model of chronic migraine (CM) using recurrent intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg), and prophylactic treatment was simulated by administering NBP (30 mg/kg, 60 mg/kg, 120 mg/kg) by gavage prior to each NTG injection. Mechanical threshold was assessed using von Frey fibers, and photophobia and anxious behaviours were assessed using a light/dark box and elevated plus maze. Expression of c-Fos, calcitonin gene-related peptide (CGRP), Nucleus factor erythroid 2-related factor 2 (Nrf2) and related pathway proteins in the spinal trigeminal nucleus caudalis (SP5C) were detected by Western blotting (WB) or immunofluorescence (IF). The expression of IL-1β, IL-6, TNF-α, Superoxide dismutase (SOD) and malondialdehyde (MDA) in SP5C and CGRP in plasma were detected by ELISA. A reactive oxygen species (ROS) probe was used to detect the expression of ROS in the SP5C.
    RESULTS: At the end of the modelling period, chronic migraine mice showed significantly reduced mechanical nociceptive thresholds, as well as photophobic and anxious behaviours. Pretreatment with NBP attenuated nociceptive sensitization, photophobia, and anxiety in the model mice, reduced expression levels of c-Fos and CGRP in the SP5C and activated Nrf2 and its downstream proteins HO-1 and NQO-1. By measuring the associated cytokines, we also found that NBP reduced levels of oxidative stress and inflammation. Most importantly, the therapeutic effect of NBP was significantly reduced after the administration of ML385 to inhibit Nrf2.
    CONCLUSIONS: Our data suggest that NBP may alleviate migraine by activating the Nrf2 pathway to reduce oxidative stress and inflammation in migraine mouse models, confirming that it may be a potential drug for the treatment of migraine.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Case Reports
    ATF6相关色盲(ACHM)是一种罕见的常染色体隐性遗传疾病,其特征是视力下降,畏光,眼球震颤,和不良的色觉。
    对一名中国ACHM患者进行了详细的眼科检查。进行全外显子组测序和Sanger测序以检测患者的致病基因。
    一个6岁的女孩出现畏光,低视力和减少颜色的辨别。观察到双眼黄斑中的小黄色病变。FAF显示黄斑中央凹的荧光不足。OCT图像显示中央凹区域的椭圆体和交叉带中断,中央凹凹陷丢失。ERG显示相对正常的杆响应和不可记录的视锥响应。测序结果鉴定了ATF6基因(NM_007348.4)中的新型剪接变体c.354+6T>C。
    我们报道了一名新的中国ATF6相关ACHM患者的详细临床特征和遗传分析。
    UNASSIGNED: ATF6-associated Achromatopsia (ACHM) is a rare autosomal recessive disorder characterized by reduction of visual acuity, photophobia, nystagmus, and poor color vision.
    UNASSIGNED: Detailed ophthalmological examinations were performed in a Chinese patient with ACHM. Whole exome sequencing and Sanger sequencing were performed to detect the disease-causing gene in the patient.
    UNASSIGNED: A 6-year-old girl presented photophobia, low vision and reduced color discrimination. Small yellow lesion in the macula of both eyes was observed. FAF demonstrated hypofluorescence in the macular fovea. OCT images revealed interruption of ellipsoid and interdigitation zone in the foveal area and a loss of the foveal pit. ERG showed relatively normal rod responses and unrecordable cone responses. Sequencing result identified a novel splicing variant c.354 + 6T>C in the ATF6 gene (NM_007348.4).
    UNASSIGNED: We reported detailed clinical features and genetic analysis of a new Chinese ATF6-associated patient with ACHM.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    目的:评价无缝线巩膜内人工晶状体(IOL)内固定联合改良虹膜环扎术治疗无晶状体眼和外伤性散瞳的安全性和有效性。
    方法:同一位外科医生对5例无晶状体眼和外伤性散瞳患者进行手术。所有患者均行无缝线巩膜内人工晶状体固定术联合改良虹膜环扎术,随访≥6个月。使用最小分辨率角(logMAR)的对数测量最佳矫正视力(BCVA)。BCVA,眼内压(IOP),瞳孔直径,术前、术后角膜内皮细胞计数(CECC)进行统计学分析。瞳孔形状,畏光,IOL位置,并对手术并发症进行了评估。
    结果:术后6个月平均BCVA明显改善(0.26±0.17logMAR,P=0.042)比术前(0.50±0.30logMAR)。术前、术后眼压差异无统计学意义(P=0.138)。术后平均瞳孔直径较术前显著减小(3.44±0.35mmvs.7.28±0.35mm,P=0.043)。术后CECC无明显下降(P=0.225)。瞳孔形状是圆形的,所有患者畏光消失。术中、术后无并发症发生。
    结论:无Sutueless巩膜内人工晶状体内固定联合改良虹膜环扎术瞳孔成形术是治疗无晶状体外伤性散瞳患者的安全有效的方法。
    OBJECTIVE: To evaluate the safety and efficacy of sutureless intrascleral intraocular lens (IOL) fixation combined with modified iris cerclage pupilloplasty for treating aphakia and traumatic mydriasis.
    METHODS: Five patients with aphakia and traumatic mydriasis were operated on by the same surgeon. All patients underwent sutureless intrascleral IOL fixation combined with modified iris cerclage pupilloplasty and were followed up for ≥6 months. Best-corrected visual acuity (BCVA) was measured using the logarithm of the minimum angle of resolution (logMAR). BCVA, intraocular pressure (IOP), pupil diameter, and corneal endothelial cell count (CECC) preoperatively and postoperatively were statistically analyzed. The pupil shape, photophobia, IOL position, and surgical complications were evaluated.
    RESULTS: The mean BCVA was significantly improved 6 months postoperatively (0.26 ± 0.17 logMAR, P = 0.042) than preoperatively (0.50 ± 0.30 logMAR). No significant difference was observed between the preoperative and postoperative IOP (P = 0.138). The mean pupil diameter significantly reduced postoperatively than preoperatively (3.44 ± 0.35 mm vs. 7.28 ± 0.35 mm, P = 0.043). There was no significant decrease in CECC postoperatively (P = 0.225). The pupil shape was round-like, and photophobia disappeared in all patients. No intraoperative or postoperative complications occurred.
    CONCLUSIONS: Sutureless intrascleral IOL fixation combined with modified iris cerclage pupilloplasty is a safe and efficient procedure for treating aphakia traumatic mydriasis patients without sufficient capsular support.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    毛囊角化病(KFSD)是一种罕见的X连锁遗传性疾病,其特征是滤泡性角化过度-畏光-脱发三联症。临床异质性使诊断困难。探讨KFSD的临床病理特征和镜下特征,进一步明确诊断的必要条件。我们对KFSD患者进行了回顾性研究.临床信息,组织学特征,和三镜检查结果进行了评估。八名患者来自七个不同的家庭。两名女性是来自同一家庭的母亲和女儿,其他六名患者是男性,代表散发病例。脱发的平均发病年龄为21.25岁。头皮毛发的参与导致头皮中线进行性瘢痕性脱发并伴有不同程度的炎症是病理特征。它通常在青春期后开始。与毛发相关的毛囊角化过度病变影响了所有患者。然而,畏光不是一个恒定的特征。组织病理学检查显示毛囊疾病伴有急慢性炎症反应。卵泡变化,包括融合漏斗,外根鞘伸入卵泡管,观察到由角蛋白闭塞引起的峡部毛囊扩张。三镜特征包括毛囊周围鳞屑,簇绒的毛发,和卵泡开口的丧失。总之,末梢毛发受累,无论是头皮毛发,眉毛,或者睫毛,绒毛毛囊角化过度是KFSD的诊断依据。我们假设组织病理学的卵泡变化是引发可变炎症和进一步卵泡破坏的主要事件。
    Keratosis follicularis spinulosa decalvans (KFSD) is a rare X-linked hereditary disorder characterized by the triad of follicular hyperkeratosis-photophobia-alopecia. The clinical heterogeneity makes the diagnosis difficult. To investigate the clinicopathologic and trichoscopic features of KFSD and to further clarify the essential requisites for the diagnosis, we conducted a retrospective study of patients with KFSD. The clinical information, histologic features, and trichoscopic findings were evaluated. Eight patients were from seven separate families. Two females were mother and daughter from the same family and the other six patients were male and represented sporadic cases. The average age of onset of alopecia was 21.25 years. Involvement of the scalp hairs leading to progressive scarring alopecia on the midline of the scalp with variable degrees of inflammation was the pathognomonic feature. It typically began after puberty. Vellus hair-associated follicular hyperkeratosis affected all of the patients. However, photophobia was not a constant feature. Histopathologic examination revealed disorders of the hair follicle with an acute-chronic inflammatory response. Follicular changes including fused infundibulum, the protrusion of the outer root sheath into the follicular canal, and a dilatation of the follicles at the isthmus level caused by the occlusion of keratin were observed. The trichoscopic features included perifollicular scaling, tufted hairs, and loss of follicular openings. In conclusion, terminal hair involvement, either scalp hairs, eyebrows, or eyelashes, and the hyperkeratosis of the follicle of vellus hairs is the diagnostic basis of KFSD. We hypothesize that follicular changes in histopathology are the primary event that trigger variable inflammation and further follicular destruction.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    作为进化上保守的细胞器,脂滴(LD)具有多种功能,并且在不同的细胞类型和物种中具有各种亚细胞定位。在鸟类视锥细胞中,有一个单一的顶部局部LD。我们证明了CIDEA(诱导DFFA样效应物a的细胞死亡)和微管促进鸡视锥细胞中单个LD的形成。Centrins,这是众所周知的中心粒蛋白,通过其C末端钙结合域靶向视锥细胞LD。Centrins在SPDL1-L(纺锤体卷曲螺旋蛋白1-L)的帮助下定位在视锥细胞LD上,动粒相关的动力蛋白衔接子SPDL1的先前未表征的同工型。CETN3的丢失或截短的CETN1的过表达取消了视锥细胞LD的顶端定位。仿真分析表明,多个LD或单个错位LD降低了光灵敏度。总的来说,我们的发现确定了centrins在视锥细胞LD定位调节中的作用,这对视锥细胞的光敏性很重要。
    As evolutionarily conserved organelles, lipid droplets (LDs) carry out numerous functions and have various subcellular localizations in different cell types and species. In avian cone cells, there is a single apically localized LD. We demonstrated that CIDEA (cell death inducing DFFA like effector a) and microtubules promote the formation of the single LD in chicken cone cells. Centrins, which are well-known centriole proteins, target to the cone cell LD via their C-terminal calcium-binding domains. Centrins localize on cone cell LDs with the help of SPDL1-L (spindle apparatus coiled-coil protein 1-L), a previously uncharacterized isoform of the kinetochore-associated dynein adaptor SPDL1. The loss of CETN3 or overexpression of a truncated CETN1 abrogates the apical localization of the cone cell LD. Simulation analysis showed that multiple LDs or a single mispositioned LD reduces the light sensitivity. Collectively, our findings identify a role of centrins in the regulation of cone cell LD localization, which is important for the light sensitivity of cone cells.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    目的:目的总结埋缝法重睑成形术中缝线外露相关角膜并发症的误诊及处理方法。
    方法:本研究回顾性分析哈尔滨医科大学附属第一医院2020年1月至2022年7月14例埋线双睑成形术后缝线外露所致的眼球结膜及角膜并发症。患者的临床症状包括畏光,流泪,疼痛,异物感,眼睑肿胀,结膜充血,分泌,等。我们记录了病人的性别,年龄,手术方法,暴露缝合线的长度,缝线类型,双眼皮手术的数量,手术部位,眼睛不适发生的时间点,误诊疾病及治疗。
    结果:3例患者被误诊为干眼症,9例患者被误诊为病毒性角膜炎,2例误诊为过敏性结膜炎。14例患者均有畏光表现,流泪,疼痛,异物感和结膜充血。8例患者有眼睑肿胀的表现。5例患者有眼部分泌物的表现。其中角膜上皮损伤8例,角膜溃疡6例。所有患者均接受了缝线移除,无进一步进展。十名患者接受了人工泪液治疗,4例患者拔线后用小牛血清去蛋白凝胶治疗。
    结论:如果埋缝重睑成形术后患者出现眼睑和角膜并发症引起的眼部不适,临床医生应认真检查是否有缝线暴露,并及时确定原因。缝合是治疗这种并发症的最佳方法。
    方法:本期刊要求作者为每篇文章分配一定程度的证据。对于这些循证医学评级的完整描述,请参阅目录或在线作者说明www。springer.com/00266.
    OBJECTIVE: The purpose of this study was to summarize the misdiagnosis and treatment of corneal complications associated with suture exposure in cases of buried-suture double-eyelid blepharoplasty.
    METHODS: This study retrospectively analyzed 14 patients with palpebral conjunctival and corneal complications due to suture exposure after buried-suture double-eyelid blepharoplasty at the First Affiliated Hospital of Harbin Medical University from January 2020 to July 2022. The patients\' clinical symptoms included photophobia, lacrimation, pain, foreign body sensation, swelling of the eyelids, conjunctival hyperemia, secretion, etc. We recorded the patient\'s sex, age, surgical method, length of exposed suture, suture type, number of double-eyelid surgeries, surgical site, timepoint when eye discomfort occurred, misdiagnosed disease and treatment.
    RESULTS: Three patients were misdiagnosed with dry eye, nine patients were misdiagnosed with viral keratitis, and two patients were misdiagnosed with allergic conjunctivitis. All 14 patients had manifestations of photophobia, lacrimation, pain, foreign body sensation and conjunctival hyperemia. Eight patients had manifestations of swelling of the eyelids. Five patients had manifestations of eye secretions. There were 8 patients with corneal epithelial injuries and 6 patients with corneal ulcers. All patients underwent suture removal without further progression. Ten patients were treated with artificial tears, and 4 patients were treated with calf serum deproteinized gel after suture removal.
    CONCLUSIONS: If there is postoperative eye discomfort caused by eyelid and corneal complications in patients after buried-suture double-eyelid blepharoplasty, clinicians should carefully check whether there is suture exposure and determine the cause in a timely manner. Suture removal is the best way to treat this complication.
    METHODS: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Systematic Review
    大量研究已经评估了低剂量阿托品在预防或减缓近视进展中的功效。然而,从这些研究中评估眼部安全性具有挑战性.我们旨在评估近视儿童阿托品引起的不良事件的发生率。我们在几个数据库中对2022年11月之前发表的研究进行了系统的文献检索。阿托品诱导的不良事件的发生率通过共同效应(固定效应)或随机效应模型进行汇总。根据药物剂量进行亚组分析,不良事件的类型和种族。最终共有31篇文章被纳入研究。阿托品不良事件的总发生率为5.9%,严重不良事件发生率为0.0%。最常见的不良事件是畏光(9.1%)和近视力模糊(2.9%)。其他不良事件,包括眼睛刺激/不适,过敏反应,头痛,style/chalazion,小于1%的患者发生眩光和头晕。阿托品引起的不良事件的发生率因药物剂量而异。较低剂量的阿托品与较低的不良事件发生率相关。亚洲儿童和白人儿童低剂量阿托品的不良事件发生率无显著差异。我们的研究表明,畏光和近视力模糊是阿托品引起的最常见的不良事件。低剂量阿托品比中等剂量和高剂量阿托品更安全。本研究可为眼科医生为近视儿童开具阿托品处方提供安全参考。本文受版权保护。保留所有权利。
    A large number of studies have evaluated the efficacy of low-dose atropine in preventing or slowing myopic progression. However, it is challenging to evaluate the ocular safety from these studies. We aimed to evaluate the incidence of adverse events induced by atropine in children with myopia. We performed a systematic literature search in several databases for studies published until November 2022. The incidence of adverse events induced by atropine was pooled by a common-effect (fixed-effect) or random-effects model. Subgroup analyses were conducted according to drug doses, types of adverse events, and ethnicity. A total of 31 articles were ultimately included in the study. The overall incidence of adverse events for atropine was 5.9%, and the incidence of severe adverse events was 0.0%. The most commonly reported adverse events were photophobia (9.1%) and blurred near vision (2.9%). Other adverse events including eye irritation/discomfort, allergic reactions, headache, stye/chalazion, glare, and dizziness occurred in less than 1% of the patients. The incidence of atropine-induced adverse events varied depending on the drug doses. A lower dose of atropine was associated with a lower incidence of adverse events. There was no significant difference in the incidence of adverse events for low-dose atropine between Asian and White children. Our study suggests photophobia and blurred near vision are the most frequently reported adverse events induced by atropine. Low-dose atropine is safer than moderate- and high-dose atropine. Our study could provide a safe reference for ophthalmologists to prescribe atropine for myopic children.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    信号肽酶(SPase)负责成熟过程中大多数分泌前体蛋白和许多膜蛋白中N末端信号肽的裂解。在这项研究中,我们在香蕉枯萎病真菌病原体镰刀菌中鉴定了SPase复合物的四个成分(FoSec11,FoSpc1,FoSpc2和FoSpc3)。我们通过双分子荧光互补(BiFC)和亲和纯化和质谱(AP-MS)测定证明了四个SPase亚基之间存在相互作用。在四个SPase基因中,FoSPC2已成功删除。FoSPC2缺失导致营养生长缺陷,分生孢子,和毒力。FoSPC2的丢失也影响了一些致病性相关的细胞外基质的分泌,这表明,不含FoSpc2的SPase在管理F.ododatissimum中胞外酶的成熟方面可能具有较低的效率。此外,我们发现ΔFoSPC2突变体对光的敏感性增加,并且突变体的菌落在全暗条件下比在全光条件下生长更快。我们进一步观察到,FoSPC2的缺失影响蓝光光感受器基因FoWC2的表达,导致FoWc2在全光条件下的细胞质积累。由于FoWc2具有信号肽,FoSpc2可能间接调控FoWc2的表达和亚细胞定位。与其对光的反应相反,ΔFoSPC2突变体对渗透胁迫的敏感性显着降低,在渗透胁迫条件下培养突变体可以恢复FoWc2的定位和ΔFoSPC2的光敏感性,这表明渗透胁迫和F.odoratissimum和FoSpc2中的光响应途径之间的串扰参与了这些过程。在这项研究中的重要性,我们在香蕉枯萎病病原体镰刀菌中鉴定了SPase的四个成分,并表征了SPaseFoSpc2。FoSPC2的丢失影响了胞外酶的分泌,这表明,不含FoSpc2的SPase在管理F.ododatissimum中胞外酶的成熟方面可能具有较低的效率。此外,这是我们第一次发现SPase与真菌光反应之间的关系。FoSPC2的缺失导致对渗透应力的敏感性降低,但对光的敏感性增加。连续光照抑制了ΔFoSPC2突变体的生长速率,并影响了该突变体中蓝光感光体FoWc2的细胞定位,但是在渗透胁迫下培养突变体既恢复了FoWc2的定位,又消除了ΔFoSPC2突变体的光敏性,这表明FoSPC2的丢失可能会影响双歧杆菌的渗透胁迫和光响应途径之间的串扰。
    Signal peptidase (SPase) is responsible for cleavage of N-terminal signal peptides in most secretory precursor proteins and many membrane proteins during maturation. In this study, we identified four components of the SPase complex (FoSec11, FoSpc1, FoSpc2, and FoSpc3) in the banana wilt fungal pathogen Fusarium odoratissimum. We proved that interactions exist among the four SPase subunits by bimolecular fluorescence complementation (BiFC) and affinity purification and mass spectrometry (AP-MS) assays. Among the four SPase genes, FoSPC2 was successfully deleted. FoSPC2 deletion caused defects in vegetative growth, conidiation, and virulence. Loss of FoSPC2 also affected the secretion of some pathogenicity-related extracellular enzymes, suggesting that SPase without FoSpc2 may have a lower efficiency in managing the maturation of the extracellular enzymes in F. odoratissimum. In addition, we found that the ΔFoSPC2 mutant had increased sensitivity to light, and the colonies of the mutant grew faster under all-dark conditions than under all-light conditions. We further observed that deletion of FoSPC2 affected expression of the blue light photoreceptor gene FoWC2, leading to cytoplasmic accumulation of FoWc2 under all-light conditions. Since FoWc2 has signal peptides, FoSpc2 may regulate the expression and subcellular localization of FoWc2 indirectly. Contrary to its response to light, the ΔFoSPC2 mutant displayed a significant decreased sensitivity to osmotic stress, and culturing the mutant under osmotic stress conditions restored both the localization of FoWc2 and light sensitivity of the ΔFoSPC2, suggesting that a cross talk between osmotic stress and light response pathways in F. odoratissimum and FoSpc2 takes part in these processes. IMPORTANCE In this study, we identified four components of SPase in the banana wilt pathogen Fusarium odoratissimum and characterized the SPase FoSpc2. Loss of FoSPC2 affected the secretion of extracellular enzymes, suggesting that SPase without FoSpc2 may have a lower efficiency in managing the maturation of the extracellular enzymes in F. odoratissimum. In addition, this is the first time that we have found a relationship between the SPase and fungal light response. Deletion of FoSPC2 resulted in decreased sensitivity to the osmotic stresses but with increased sensitivity to light. Continuous light inhibited the growth rate of the ΔFoSPC2 mutant and affected the cellular localization of the blue light photoreceptor FoWc2 in this mutant, but culturing the mutant under osmotic stress both restored the localization of FoWc2 and eliminated the light sensitivity of the ΔFoSPC2 mutant, suggesting that loss of FoSPC2 may affect a cross talk between the osmotic stress and light response pathways in F. odoratissimum.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:偏头痛是一种具有多种症状的高度致残的健康负担;然而,由于对其神经机制的理解不足,它仍然没有得到充分的治疗。神经肽Y(NPY)已被证明参与调节疼痛和情绪,并可能在偏头痛的病理生理学中起作用。在偏头痛患者中发现了NPY水平的变化,但是这些变化是否以及如何导致偏头痛是未知的。因此,本研究的目的是探讨NPY在偏头痛样表型中的作用.
    方法:这里,我们使用腹腔注射硝酸甘油酯(GTN,10mg/kg)作为偏头痛小鼠模型,通过光线厌恶测试验证了这一点,冯·弗雷测试,和高架加迷宫测试。然后,我们用NPY-GFP小鼠进行全脑成像,以探索通过GTN治疗改变NPY的关键区域。接下来,我们将NPY显微注射到内囊(MHb)中,并进一步将Y1或Y2受体激动剂注入MHb,分别,检测NPY在GTN诱导的偏头痛样行为中的作用。
    结果:GTN有效触发异常性疼痛,畏光,和老鼠的焦虑样行为。之后,我们发现GTN处理小鼠的MHb中GFP+细胞水平降低。NPY的显微注射减轻了GTN诱导的异常性疼痛和焦虑,而不影响畏光。此外,我们发现激活Y1-而非Y2-受体可减弱GTN诱导的异常性疼痛和焦虑。
    结论:综合来看,我们的数据支持MHb中的NPY信号通过Y1受体产生镇痛和抗焦虑作用.这些发现可能为偏头痛的治疗提供新的治疗靶点。
    BACKGROUND: Migraine is a highly disabling health burden with multiple symptoms; however, it remains undertreated because of an inadequate understanding of its neural mechanisms. Neuropeptide Y (NPY) has been demonstrated to be involved in the modulation of pain and emotion, and may play a role in migraine pathophysiology. Changes in NPY levels have been found in patients with migraine, but whether and how these changes contribute to migraine is unknown. Therefore, the purpose of this study was to investigate the role of NPY in migraine-like phenotypes.
    METHODS: Here, we used intraperitoneal injection of glyceryl trinitrate (GTN, 10 mg/kg) as a migraine mouse model, which was verified by light-aversive test, von Frey test, and elevated plus maze test. We then performed whole-brain imaging with NPY-GFP mice to explore the critical regions where NPY was changed by GTN treatment. Next, we microinjected NPY into the medial habenula (MHb), and further infused Y1 or Y2 receptor agonists into the MHb, respectively, to detect the effects of NPY in GTN-induced migraine-like behaviors.
    RESULTS: GTN effectively triggered allodynia, photophobia, and anxiety-like behaviors in mice. After that, we found a decreased level of GFP+ cells in the MHb of GTN-treated mice. Microinjection of NPY attenuated GTN-induced allodynia and anxiety without affecting photophobia. Furthermore, we found that activation of Y1-but not Y2-receptors attenuated GTN-induced allodynia and anxiety.
    CONCLUSIONS: Taken together, our data support that the NPY signaling in the MHb produces analgesic and anxiolytic effects through the Y1 receptor. These findings may provide new insights into novel therapeutic targets for the treatment of migraine.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号