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Capillary Red Blood Cell Velocity Is Decreased in Skeletal Muscle of Septic Rats: In Vivo Imaging Using Videocapillaroscopy. 脓毒症大鼠骨骼肌毛细血管红细胞速度降低:用视频毛细血管镜在体内成像。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-10389-5_16
Rin Kataoka, Naoki Hitosugi, Kazuki Hotta, Narumi Fukuzaki, Kota Izawa, Shuri Arai, Tomotaka Koike, Kentaro Kamiya, Atsuhiko Matsunaga

This study aimed to investigate the impact of sepsis on red blood cell (RBC) velocity, diameter, and categories of skeletal muscle capillaries 3-4 h after sepsis onset. Male Wistar rats (9-11 weeks old, n = 14) were randomly classified into sham and cecal ligation and perforation (CLP) groups, respectively. In vivo imaging of capillaries in the spinotrapezius muscle was performed using stain-free videocapillaroscopy. RBC velocity and capillary diameter were analyzed. Capillaries were classified into three groups: (1) continuously flowing capillaries defined as maintaining continuous flow for >30 s; (2) intermittently flowing, showing brief stagnation lasting <10 s; (3) stopped-flow, showing no flow for >10 s during 30 s of observation periods. The number of capillaries in each category is compared between the groups. The RBC velocity of the CLP group was significantly lower than that of the sham group (p = 0.01), but the capillary diameter was not different between the groups. The CLP group showed a trend of a weak negative correlation between capillary diameter and RBC velocity (r2 = 0.16, p = 0.08), but the sham group did not. No significant difference was observed between the groups in each capillary category. These results suggest that sepsis decreases RBC velocity in resting skeletal muscle capillaries but has no effect on capillary category or diameter.

本研究旨在探讨脓毒症发病后3-4小时对骨骼肌毛细血管红细胞(RBC)速度、直径和种类的影响。雄性Wistar大鼠(9 ~ 11周龄,n = 14)随机分为假手术组和盲肠结扎穿孔组。使用无染色的视频毛细血管镜对斜方肌的毛细血管进行体内成像。分析红细胞流速和毛细血管直径。将毛细血管分为三组:(1)连续流动毛细血管,定义为连续流动bbb30 s;(2)间歇流动,在30 s的观测周期内表现为10 s的短暂停滞。比较各组之间的毛细血管数量。CLP组红细胞流速显著低于假手术组(p = 0.01),毛细血管直径组间差异无统计学意义。CLP组毛细血管直径与红细胞流速呈弱负相关(r2 = 0.16, p = 0.08),假手术组无此趋势。各毛细血管类别组间差异无统计学意义。这些结果表明,脓毒症降低静息骨骼肌毛细血管的红细胞速度,但对毛细血管种类和直径没有影响。
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引用次数: 0
Net Water Uptake and Cerebral Microcirculation in Perilesional Penumbra in TBI: CT Perfusion Study. TBI病灶周围半暗区净吸水和脑微循环:CT灌注研究。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-10389-5_28
Alex O Trofimov, Ilya Kochsheev, George Kalentyev, Ekaterina Volkova, Edwin M Nemoto, Olga Bragina, Denis E Bragin

The aim of our study was to compare brain tissue net water uptake (NWU), cerebral oxygenation, and microcirculation changes in perilesional penumbra foci (PPF) in moderate isolated traumatic brain injury (moiTBI) patients.

Materials and methods: 77 moiTBI patients (women 35; men 42, age 37 years [34;39]) with unilateral frontal/frontotemporal lesions (Marshall II-III) were included in this retrospective, non-randomized, single-center study. Perfusion parameters were measured in PPF zones and determined using multiphase perfusion computed tomography (PCT) in the first 2 days after trauma and admission. NWU in hypoattenuated perilesional zones was calculated using non-contrast CT. Cerebral oxygenation (SctO2) was simultaneously measured using near-infrared spectroscopy in the frontal lobes with PCT. Data are shown as a median [interquartile range]. Statistical analysis was performed using nonparametric statistics. P < 0.05 was considered statistically significant.

Results: In PPF, SctO2 was 64.03% [60.1;67.0], cerebral blood flow (CBF) was 30.6 ml/100 g/min [22.3; 38.7], cerebral blood volume (CBV) was 2 ml/100 g [1.6; 2.5], mean transit time (MTT) was 4.8 s [4.1;5.8], time to peak (TTP) was 21.8 s [20;24.2], NWU was 4.98% [2.21;7.39]. CBF, CBV, and SctO2 in PPF were significantly lower; MTT was more prolonged than in non-damaged tissue (p < 0.001). Increased NWU values in PPF were significantly correlated with CBV (r = 0.723, p < 0.001); CBF (r = -0.228, p = 0.048), TTP (r 0.225, p = 0.047), and SctO2 (r = -0.608, p < 0.001). There were no significant correlations between NWUPPF and MTT.

Conclusions: Brain edema in PPF was significantly associated with cerebral microcirculation and cerebral O2 saturation disturbances in moiTBI.

本研究的目的是比较中度孤立性创伤性脑损伤(moiTBI)患者的脑组织净吸水(NWU)、脑氧合和病灶周围半暗灶(PPF)的微循环变化。材料和方法:这项回顾性、非随机、单中心研究纳入了77例伴有单侧额叶/额颞叶病变(Marshall II-III)的moiTBI患者(女性35岁,男性42岁,年龄37岁[34;39])。在创伤和入院后的前2天,在PPF区测量灌注参数,并使用多相灌注计算机断层扫描(PCT)确定灌注参数。使用非对比CT计算低衰减性病变周围区的NWU。脑氧合(SctO2)同时通过近红外光谱在前额叶与PCT测量,数据显示为中位数[四分位数范围]。采用非参数统计进行统计分析。结果:PPF患者SctO2为64.03%[60.1;67.0],脑血流量(CBF)为30.6 ml/100 g/min [22.3;38.7],脑血容量(CBV)为2 ml/100 g [1.6;平均穿越时间(MTT)为4.8 s[4.1;5.8],到达峰值时间(TTP)为21.8 s [20,24.2], NWU为4.98%[2.21;7.39]。PPF患者CBF、CBV、SctO2显著降低;MTT较未损伤组织延长(p 2 (r = -0.608, p PPF与MTT)。结论:PPF脑水肿与moiTBI脑微循环和脑氧饱和度紊乱有显著相关性。
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引用次数: 0
Mind the Individual: Physiological Reactions to Long-Term Colored Light Exposure Assessed by SPA-fNIRS (Knisely Award Honorary Lecture). 关注个体:用SPA-fNIRS评估长期接触有色光的生理反应(knely奖荣誉讲座)。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-10389-5_2
Hamoon Zohdi, Felix Scholkmann, Ursula Wolf

Colored light exposure (CLE) is a common occurrence in everyday life. In today's modern society, we are increasingly exposed to various sources of colored light, including advertisements, computer and smartphone displays, energy-saving light bulbs, private settings, and street lighting with LEDs. Therefore, the effects of colored light on human physiology are becoming a subject of growing interest to both the research community and society. To gain a deeper understanding of the complex effects of long-term CLE on the human body, we have conducted a series of pioneering studies (with results published in 16 papers) over the past 8 years using the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. This approach facilitates concurrent brain activity measurement using fNIRS alongside multiple systemic physiological parameters. Our studies yielded a number of new findings: (i) We discovered the need for both group-level and individual-level analyses to fully understand the effects of CLE on human physiology. (ii) We found that CLE has relatively long-lasting effects on cerebrovascular and systemic physiology in humans. (iii) Yellow and short-wavelength light (i.e., blue and violet) were found to induce higher brain activation in the prefrontal cortex and visual cortex, respectively, compared to other colored lights (e.g., red, orange, and green). (iv) We observed that healthy adults exhibited a range of different types of physiological responses. Machine learning enabled us to classify the response patterns and provide new insights into the common response patterns between subjects. Given the rapid exposure of our society to new and increasing lighting levels, this research's findings are of interest and relevance to the scientific community, medical professionals, and society.

彩色光暴露(CLE)是日常生活中常见的现象。在当今的现代社会中,我们越来越多地接触到各种各样的彩色光源,包括广告、电脑和智能手机显示屏、节能灯泡、私人环境和led路灯。因此,有色光对人体生理的影响正成为研究界和社会日益关注的课题。为了更深入地了解长期CLE对人体的复杂影响,我们在过去8年中使用系统生理增强功能近红外光谱(SPA-fNIRS)方法进行了一系列开创性研究(结果发表在16篇论文中)。这种方法有助于使用fNIRS和多个系统生理参数同时测量大脑活动。我们的研究产生了一些新的发现:(i)我们发现需要在群体水平和个人水平上进行分析,以充分了解CLE对人体生理的影响。(ii)我们发现CLE对人类脑血管和全身生理有相对持久的影响。(iii)与其他颜色的光(如红色、橙色和绿色)相比,黄色和短波长的光(即蓝色和紫色)分别在前额叶皮层和视觉皮层诱导更高的大脑激活。(iv)我们观察到健康成人表现出一系列不同类型的生理反应。机器学习使我们能够对反应模式进行分类,并对受试者之间的常见反应模式提供新的见解。鉴于我们的社会快速暴露于新的和不断增加的照明水平,这项研究的发现对科学界、医学专业人士和社会都很有兴趣和相关性。
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引用次数: 0
Unlocking Unique Physiological Reactions: Novel Insights into Four Cerebral and Systemic Physiological Responses to Colored Light. 解锁独特的生理反应:对四种大脑和系统对彩色光的生理反应的新见解。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-10389-5_22
Hamoon Zohdi, Sarusan Jegatheeswaran, Felix Scholkmann, Ursula Wolf

Background: For several years, our research group has been systematically investigating how changes in cerebral hemodynamics as well as systemic physiology can be induced by colored light exposure (CLE). We have observed that these physiological changes can differ between subjects for exactly the same CLE stimulus. In the present case series, we report specific physiological reactivity patterns from four subjects.

Methods: A total of 36 subjects participated in the study. These subjects were exposed to blue and red light while performing a 2-back task. For the present analysis, we selected four subjects as representative examples of distinct response patterns. We simultaneously measured changes in cerebral and systemic physiological parameters using the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) method. The SPA-fNIRS method included oxygenated hemoglobin ([O2Hb]) and deoxygenated hemoglobin ([HHb]) in the prefrontal cortex, mean arterial pressure (MAP), end-tidal carbon dioxide (PETCO2), skin conductance level (SCL), and respiration rate (RR).

Results: We identified four distinct patterns of physiological responses. Pattern 1: For all parameters except MAP, the subject's response to blue and red light remained consistent. Pattern 2: Similar to the previous case, there was no significant contrast between red and blue with respect to changes in cerebral hemodynamics. Similar patterns were also detected for PETCO2 and MAP, whereas completely different patterns were found for SCL. Surprisingly, an inverse correlation was found for RR. Pattern 3: Changes in most parameters exhibited mirrored effects. Consistent trends were observed for SCL and RR. Pattern 4: Mirrored patterns were observed for [O2Hb] and [HHb], the same patterns for PETCO2 and RR, and divergent trends for MAP and SCL.

Conclusions: In our analysis of SPA-fNIRS measurements, we identified four subjects with specific physiological reactivity patterns to a combined CLE and cognitive task. Individual physiological reactivity or physiological constitution should be taken into account when analyzing physiological data on CLE to enable a more adequate interpretation of the results.

背景:多年来,我们的研究小组一直在系统地研究彩色光照射(CLE)如何诱导脑血流动力学和全身生理学的变化。我们已经观察到,对于完全相同的CLE刺激,这些生理变化在受试者之间是不同的。在本病例系列中,我们报告了四个受试者的特定生理反应模式。方法:共36名受试者参与研究。这些受试者在执行双背任务时暴露在蓝光和红光下。在目前的分析中,我们选择了四个受试者作为不同反应模式的代表性例子。我们使用系统生理增强功能近红外光谱(SPA-fNIRS)方法同时测量了大脑和全身生理参数的变化。SPA-fNIRS方法包括前额叶皮层的含氧血红蛋白([O2Hb])和脱氧血红蛋白([hbb])、平均动脉压(MAP)、潮末二氧化碳(PETCO2)、皮肤电导水平(SCL)和呼吸速率(RR)。结果:我们确定了四种不同的生理反应模式。模式1:除MAP外,受试者对蓝光和红光的反应保持一致。模式2:与前一例相似,在脑血流动力学变化方面,红色和蓝色之间没有明显的对比。PETCO2和MAP也检测到类似的模式,而SCL则发现完全不同的模式。令人惊讶的是,RR呈负相关。模式3:大多数参数的变化表现出镜像效应。SCL和RR的趋势一致。模式4:[O2Hb]和[hbb]呈镜像模式,PETCO2和RR呈相同模式,MAP和SCL呈发散趋势。结论:在我们对SPA-fNIRS测量结果的分析中,我们确定了四名受试者对CLE和认知联合任务具有特定的生理反应模式。在分析CLE的生理数据时,应考虑个体的生理反应性或生理构成,以使结果得到更充分的解释。
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引用次数: 0
Introducing D3: A Novel Molecular Modeling Suite. 介绍D3:一个新的分子建模套件。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-03402-1_38
Eleni Papakonstantinou, Theofilos Mylonas, George Papazidis, George P Chrousos, Dimitrios Vlachakis

The rapid advancement in molecular biology and bioinformatics has enabled the development of sophisticated software tools for protein modeling and optimization. This chapter presents the development and application of a novel software suite, "D3," designed for 3D protein modeling and optimization, utilizing advanced computational techniques. The study provides a comprehensive overview of the methodology, implementation, and results obtained from applying the software in a laboratory environment. The findings demonstrate the effectiveness of the tool in accurately predicting protein structures, paving the way for future applications in drug design and molecular biology research.

分子生物学和生物信息学的快速发展使得复杂的蛋白质建模和优化软件工具的发展成为可能。本章介绍了一种新型软件套件“D3”的开发和应用,该软件是利用先进的计算技术为3D蛋白质建模和优化设计的。该研究提供了在实验室环境中应用该软件的方法、实现和结果的全面概述。这一发现证明了该工具在准确预测蛋白质结构方面的有效性,为未来在药物设计和分子生物学研究中的应用铺平了道路。
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引用次数: 0
The Determination of Physiological Variables Using a Local Analysis of Gravitational Resonances. 利用引力共振的局部分析确定生理变量。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-03402-1_13
Michael Harney, Michael Weber, Brian Nordberg, Ingrid Rauter

The measurement of the long wavelengths of the Earth's gravitational resonances with a high-sensitivity accelerometer as these resonances pass through materials of different densities enables the measurement of the relative concentration levels of organic compounds in biological specimens. This method is demonstrated in the microscale measurement of the physiologically important variables in the Chlorophyta phyla. Future analysis includes the measurement of physiological variables in humans.

当地球引力共振穿过不同密度的材料时,用高灵敏度加速度计测量地球引力共振的长波,可以测量生物标本中有机化合物的相对浓度水平。该方法已在藻门重要生理变量的微尺度测量中得到验证。未来的分析包括对人体生理变量的测量。
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引用次数: 0
Prenatal Opioid Exposure and Neonatal Opioid Withdrawal Syndrome. 产前阿片类药物暴露与新生儿阿片类药物戒断综合征。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-12741-9_12
Alana Painter, Kathryn Westphal, Adriana Herrera, Emilee Lewis, Alison Sweeney, Ashley G Sutton

Maternal substance use during pregnancy exposes the fetus to pharmacologic effects and creates the potential for dependence and withdrawal in the neonatal period. Opioids cross the placenta and the fetal blood-brain barrier, resulting in prenatal opioid exposure (POE). The binding of opioids to developing opioid receptors disrupts neurologic, gastrointestinal, and autonomic regulation, leading to the development of neonatal opioid withdrawal syndrome (NOWS), previously referred to as neonatal abstinence syndrome (NAS). The impact of exposure varies by opioid type, dose, duration, and maternal metabolism, resulting in a wide spectrum of neonatal symptoms and severity.In response to the rising incidence of NOWS during the heroin epidemic, scoring systems, including the Finnegan scale, were developed to guide diagnosis and treatment. Infants with POE whose Finnegan scores reached a particular threshold were treated with pharmacologic therapy (typically morphine), which required a prolonged taper. A more recently defined approach, the Eat, Sleep, Console method, focuses on functional well-being rather than a numeric score. Current best practice for management emphasizes non-pharmacologic interventions such as caregiver presence, skin-to-skin care, and a low-stimulation environment, and reserves pharmacologic therapy for severe symptoms.While short-term effects of POE are well documented, including prolonged hospitalization and feeding challenges, long-term neurodevelopmental and behavioral outcomes remain under investigation. Further research is essential to refine screening, optimize management strategies, standardize care, and address social and health disparities affecting families impacted by POE.

孕妇在怀孕期间使用药物会使胎儿暴露在药物作用下,并在新生儿期产生依赖和戒断的可能性。阿片类药物通过胎盘和胎儿血脑屏障,导致产前阿片类药物暴露(POE)。阿片样物质与发育中的阿片样物质受体的结合破坏神经、胃肠和自主调节,导致新生儿阿片样物质戒断综合征(NOWS)的发展,以前称为新生儿戒断综合征(NAS)。暴露的影响因阿片类药物类型、剂量、持续时间和母体代谢而异,导致广泛的新生儿症状和严重程度。为了应对海洛因流行期间NOWS发病率的上升,开发了评分系统,包括Finnegan量表,以指导诊断和治疗。芬尼根评分达到特定阈值的POE婴儿接受药物治疗(通常是吗啡),这需要长时间的逐渐减少。最近定义的一种方法,饮食,睡眠,控制台方法,侧重于功能健康,而不是数字分数。目前的最佳管理实践强调非药物干预,如护理人员在场、皮肤对皮肤护理和低刺激环境,并保留对严重症状的药物治疗。虽然POE的短期影响有充分的记录,包括延长住院时间和喂养困难,但长期的神经发育和行为结果仍在调查中。进一步的研究对于完善筛查、优化管理策略、标准化护理和解决影响POE家庭的社会和健康差异至关重要。
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引用次数: 0
Cardiomyopathy in an Adolescent with McLeod Syndrome: Searching Beyond the Routine Assessment. 青少年麦克劳德综合征心肌病:常规评估之外的搜索。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-03402-1_12
Sophie I Mavrogeni, Kyriaki Kekou, George Markousis-Mavrogenis, Flora Bacopoulou, Maria Akrioti, Maria Svingou, Joanne Traeger-Synodinos, Anna Dagouloudi, Stylianos Lafioniatis, Antigoni Papavasiliou

There are only few reports in the literature regarding McLeod Syndrome and cardiomyopathy and all of them are referred to adults with neurological symptoms and hyperCKemia. To our knowledge, this is the first reported case of a neurologically asymptomatic 14-year-old male adolescent with hyperCKemia and dilated cardiomyopathy, due to McLeod syndrome. In our patient, the documentation of clinical suspicion of McLeod syndrome was achieved by genetic assessment. Our clinical awareness guided the decision to perform a cardiovascular magnetic resonance (CMR) evaluation although the echocardiogram was normal. The lack of neurological symptoms can be attributed to the young age of the patient, since neurological symptoms usually start from 25 to 60 years of age. However, nothing is known about the age of cardiomyopathy development. Again, there is no evidence from the literature that dilated cardiomyopathy can precede the development of neurological symptoms. There is only one case in the literature presenting the coexistence of dilated cardiomyopathy, due to myocarditis and McLeod syndrome, but in our patient no history of myocarditis was identified and the CMR showed lack of myocardial oedema, indicative of myocarditis.

文献中关于麦克劳德综合征和心肌病的报道很少,而且都是指有神经系统症状和高血凝症的成年人。据我们所知,这是第一例神经系统无症状的14岁男性青少年高血钾和扩张性心肌病,由于麦克劳德综合征。在我们的病人中,临床怀疑麦克劳德综合征的文件是通过遗传评估获得的。尽管超声心动图正常,但我们的临床意识指导了进行心血管磁共振(CMR)评估的决定。没有神经系统症状可归因于患者年龄小,因为神经系统症状通常从25岁到60岁开始。然而,我们对心肌病发病的年龄一无所知。同样,文献中没有证据表明扩张性心肌病可以先于神经系统症状的发展。文献中仅有一例因心肌炎和McLeod综合征合并出现扩张型心肌病,但本例患者未发现心肌炎病史,CMR显示心肌无水肿,提示心肌炎。
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引用次数: 0
EEGs, Neuropsychological Performance and Financial Capacity in aMCI Patients: a Preliminary Longitudinal Study. aMCI患者的脑电图、神经心理表现和财务能力:一项初步的纵向研究。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-03402-1_2
Vaitsa Giannouli, Eirini Chrisovalantou Leliopoulou, Ioanna Chouvarda, Magda Tsolaki

Given the lack of relevant research, the goal of this paper is to present longitudinal data regarding electroencephalograms (EEGs) and financial capacity for amnestic mild cognitive impairment (aMCI) patients in order to examine if there are specific EEG indicators that may reveal financial capacity deficits. A detailed neuropsychological and financial capacity assessment along with EEGs was performed at three time points (baseline, 6-month retest, and 12-month retest). Strong statistically significant correlations were found exclusively for the group of aMCI patients with the lowest financial capacity performance (F1 group) between neuropsychological test performance and EEG recordings. EEGs differentiate aMCI patients into two groups: those with high financial capacity performance and those who fail in financial capacity. For the second group, EEGs measurements can be a promising source of information for predicting those aMCI individuals who need assistance in this complex cognitive domain and in order to prevent financial exploitation.

鉴于缺乏相关研究,本文的目的是通过对健忘轻度认知障碍(aMCI)患者的脑电图(EEG)和经济能力的纵向数据进行分析,以探讨是否存在特定的脑电图指标可以揭示经济能力缺陷。在三个时间点(基线、6个月复测和12个月复测)进行详细的神经心理和财务能力评估以及脑电图。仅在财务能力表现最低的aMCI患者组(F1组),神经心理测试成绩与脑电图记录之间存在显著的统计学相关性。脑电图将aMCI患者分为两组:具有高财务能力表现的患者和财务能力不佳的患者。对于第二组,脑电图测量可以是一个有希望的信息来源,用于预测那些在这个复杂的认知领域需要帮助的aMCI个体,以防止经济剥削。
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引用次数: 0
The Role of the Hedgehog Pathway in Alcohol-Induced Birth Defects. Hedgehog通路在酒精诱导出生缺陷中的作用
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-12741-9_3
Xiaojia Ji, Esraa Salim, Michael Tarpley, Cassandra Duncan, Dina Abu Rabe, Gregory J Cole, Kevin P Williams

In this chapter, we review the current literature that focuses on the role of Sonic hedgehog (Shh) signaling, a major morphogenic pathway regulating embryonic development, in the pathology of fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure (PAE). Ethanol exposure disrupts Shh signaling during development across a range of species including in mice, chick, and zebrafish. Ethanol appears to interfere with Shh signaling through multiple mechanisms, both direct and indirect, including reduced Shh ligand production, impaired post-translational processing, and inducing apoptosis in Shh-expressing cells during gastrulation. These disruptions result in a spectrum of developmental defects characteristic of FASD, such as craniofacial abnormalities, brain malformations, and limb deformities. Genetic susceptibility to PAE is linked to mutations in Shh pathway components. Activation of Shh signaling, genetically or pharmacologically, has been effective in mitigating ethanol-induced defects. This chapter also examines the teratogenic effects of cannabinoids (CBs) and ethanol, which synergistically disrupt Shh signaling. CBs directly interact with Smoothened, a key Shh receptor, amplifying developmental defects when combined with ethanol exposure. This chapter details the critical role of Shh signaling in embryogenesis and its vulnerability to environmental teratogens such as ethanol and CBs.

在本章中,我们回顾了目前的文献,重点关注Sonic hedgehog (Shh)信号在胎儿酒精谱系障碍(FASD)病理中的作用,Shh是调节胚胎发育的主要形态发生途径,由产前酒精暴露(PAE)引起。乙醇暴露会破坏包括小鼠、小鸡和斑马鱼在内的一系列物种发育过程中的Shh信号。乙醇似乎通过多种直接和间接的机制干扰Shh信号,包括减少Shh配体的产生,破坏翻译后加工,诱导原肠形成过程中表达Shh的细胞凋亡。这些破坏导致FASD的一系列发育缺陷,如颅面异常、脑畸形和肢体畸形。PAE的遗传易感性与Shh通路成分的突变有关。激活Shh信号,从遗传学或药理学上来说,在减轻乙醇诱导的缺陷方面是有效的。本章还研究了大麻素(CBs)和乙醇的致畸作用,它们协同破坏Shh信号。CBs直接与Smoothened(一种关键的Shh受体)相互作用,当与乙醇接触时,会放大发育缺陷。本章详细介绍了Shh信号在胚胎发生中的关键作用及其对环境致畸物(如乙醇和CBs)的脆弱性。
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引用次数: 0
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