AIMS Molecular Science最新文献_第5页

Genotypic and phenotypic variability of 22q11.2 microdeletions - an institutional experience. 22q11.2微缺失的基因型和表型变异-一个机构经验。

IF 1.4

AIMS Molecular Science

Pub Date : 2021-01-01 Epub Date: 2021-12-09 DOI: 10.3934/molsci.2021020

Gabrielle C Manno, Gabrielle S Segal, Alexander Yu, Fangling Xu, Joseph W Ray, Erin Cooney, Allison D Britt, Sunil K Jain, Randall M Goldblum, Sally S Robinson, Jianli Dong

Patients with chromosome 22q11.2 deletion syndromes classically present with variable cardiac defects, parathyroid and thyroid gland hypoplasia, immunodeficiency and velopharyngeal insufficiency, developmental delay, intellectual disability, cognitive impairment, and psychiatric disorders. New technologies including chromosome microarray have identified smaller deletions in the 22q11.2 region. An increasing number of studies have reported patients presenting with various features harboring smaller 22q11.2 deletions, suggesting a need to better elucidate 22q11.2 deletions and their phenotypic contributions so that clinicians may better guide prognosis for families. We identified 16 pediatric patients at our institution harboring various 22q11.2 deletions detected by chromosomal microarray and report their clinical presentations. Findings include various neurodevelopmental delays with the most common one being attention deficit hyperactivity disorder (ADHD), one reported case of infant lethality, four cases of preterm birth, one case with dual diagnoses of 22q11.2 microdeletion and Down syndrome. We examined potential genotypic contributions of the deleted regions.

22q11.2染色体缺失综合征患者典型表现为变异性心脏缺陷、甲状旁腺和甲状腺发育不全、免疫缺陷和腭咽功能不全、发育迟缓、智力残疾、认知障碍和精神障碍。包括染色体微阵列在内的新技术已经在22q11.2区域发现了较小的缺失。越来越多的研究报道，患者表现出各种特征，其中包含较小的22q11.2缺失，这表明需要更好地阐明22q11.2缺失及其表型贡献，以便临床医生更好地指导家庭预后。我们在我们的机构中发现了16例通过染色体微阵列检测到各种22q11.2缺失的儿科患者，并报告他们的临床表现。研究结果包括各种神经发育迟缓，最常见的是注意缺陷多动障碍(ADHD)， 1例婴儿死亡，4例早产，1例22q11.2微缺失和唐氏综合症的双重诊断。我们检查了缺失区域的潜在基因型贡献。

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引用次数: 2

Genetic etiology of cleft lip and cleft palate 唇腭裂的遗传病因

IF 1.4

AIMS Molecular Science

Pub Date : 2020-09-07 DOI: 10.3934/MOLSCI.2020016

Aneela Khan, C. Prashanth, N. Srinath

Genetic studies in humans have demonstrated that Cleft lip with or without cleft palate (CL/P) have a diverse genetic background and probably environmental factors influencing these malformations. CL/P is one of the most common congenital birth defects in the craniofacial region with complex etiology involving multiple genetic factors, environmental factors and gene-environment interaction. Children born with these defects suffer from various difficulties such as difficulty in speech, hearing, feeding and other psychosocial problems, and their rehabilitation involves a multidisciplinary approach. The article describes the brief introduction of CL/P, epidemiology and general concepts, etiological factors, and the genes implicated in the etiology of nonsyndromic CL/P (NSCL/P) as suggested by different human genetic studies, animal models, and other expression studies.

对人类的遗传学研究表明，伴有或不伴有腭裂的唇腭裂（CL/P）具有不同的遗传背景，可能还有影响这些畸形的环境因素。CL/P是颅面区最常见的先天性出生缺陷之一，病因复杂，涉及多种遗传因素、环境因素和基因环境相互作用。出生时有这些缺陷的儿童会遇到各种困难，如言语、听力、进食困难和其他心理社会问题，他们的康复需要多学科的方法。本文简要介绍了CL/P、流行病学和一般概念、病因以及不同人类遗传学研究、动物模型和其他表达研究提出的与非综合征性CL/P（NSCL/P）病因相关的基因。

引用次数: 11

Isolation of naringinase producing soil bacteria from Psidium guajava L. and Terminalia chebula Retz and its enzymatic activity 番石榴和慈姑中产柚皮苷酶土壤细菌的分离及其酶活性研究

IF 1.4

AIMS Molecular Science

Pub Date : 2020-07-23 DOI: 10.3934/MOLSCI.2020014

Kabyashree Phukan, D. Kardong

In commercial citrus juice, bitterness causes serious challenges in fruit juice manufacturing industries. The prime cause of bitterness is due to the presence of naringin compound. It is noted that microbial enzyme retains some specific catalytic reactions of physicochemical and biological properties possessing high degree of industrial and medical applications. The microbial enzyme naringinase can be immobilized for industrial use to reduce the cost of debittering of juice. Since environment friendly industrial biocatalysts are economically more viable, so the focus on the present study is debittering of juice at low cost without using chemicals which alter the nutrient composition. In the present study, four strains of naringin degrading bacteria were isolated from the soil of Psidium guajava L. and Terminalia chebula Retz in Dibrugarh University Botanical Garden and were investigated for naringinase activity of soil microbes and their growth conditions at different parameters. The turbidity of cell culture and concentration of proteins in the culture media have been utilized for the optimization of various growth conditions, like temperature and pH for microbial growth. The optimal growth of the four isolates was observed in a media of pH 6 and selected for further study. All the four isolates showed good extracellular naringinase activity. Among the four isolates, oval and rod shaped gram positive bacteria showed the highest specific activity (405.31 U/mg) and lowest activity was shown by rod shaped gram negative bacteria (231.77 U/mg). Furthermore, rod shaped isolate exhibited maximum growth and highest protein content among the four isolates. These results suggested that in addition to the naringinase enzyme, some other proteins were also produced by the isolates. These proteins might have some significance in supporting the growth of the microorganisms.

在商品柑桔汁中，苦味给果汁制造行业带来了严峻的挑战。苦味的主要原因是柚皮苷化合物的存在。值得注意的是，微生物酶保留了一些具有物理化学和生物特性的特定催化反应，具有高度的工业和医疗应用。将微生物酶柚皮苷酶固定化用于工业生产，可以降低果汁脱酸的成本。由于环境友好型工业生物催化剂在经济上更可行，因此目前研究的重点是在不使用改变营养成分的化学物质的情况下以低成本对果汁进行脱酸。本研究从Dibrugarh大学植物园瓜爪牙蕨(Psidium guajava L.)和chebula Terminalia Retz土壤中分离出4株柚皮苷降解菌，对土壤微生物的柚皮苷酶活性及其在不同参数下的生长条件进行了研究。利用细胞培养的浊度和培养基中蛋白质的浓度来优化微生物生长的各种生长条件，如温度和pH。在pH为6的培养基中观察到4株菌株的最佳生长情况，并选择进行进一步研究。4个菌株均表现出良好的胞外柚皮酶活性。其中，卵形和棒状革兰氏阳性菌比活性最高，为405.31 U/mg，棒状革兰氏阴性菌比活性最低，为231.77 U/mg。杆状分离物生长最快，蛋白质含量最高。这些结果表明，该菌株除了产生柚皮苷酶外，还产生了其他一些蛋白质。这些蛋白质可能对支持微生物的生长有一定的意义。

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引用次数: 1

Features, roles and chiral analyses of proteinogenic amino acids 蛋白质生成氨基酸的特征、作用及手性分析

IF 1.4

AIMS Molecular Science

Pub Date : 2020-07-02 DOI: 10.3934/molsci.2020011

N. Ayon

Amino acids (AAs) are important biomolecules responsible for plethora of functions in both prokaryotic and eukaryotic systems. There are 22 naturally occurring amino acids, among which 20 common amino acids appear in the genetic code and known as proteinogenic amino acids, which are the building blocks of proteins. Proteinogenic amino acids exist in two isomeric forms (except glycine) and the biological activity is often attributed to a specific stereoisomer. Most of the amino acids found in protein is predominantly L-AAs. A few D-amino acids can be found in bacterial cell wall, some marine invertebrates and higher organisms including frog, snail, spider, rat, chicken and human. Besides their role in protein synthesis, different proteinogenic amino acid stereoisomers have found to perform important biological roles either by functioning as precursors of a myriad of other bioactive molecules or by indicating several biological phenomena i.e. acting as markers for different physiological conditions. Given the biological importance of L- and D-amino acids (AAs), improved analytical methods for their resolution and accurate quantification remain of keen interest. Chiral analysis of amino acids in complex biological matrices poses numerous analytical challenges that are exacerbated by broad differences in polarity and ionization efficiencies of the proteinogenic amino acid stereoisomers. To date, various analytical methods are reported for chiral amino acid analysis including chromatographic, spectrometric, enzymatic, fluidic, electrophoretic and microbiological techniques. Advances in stationary phase, derivatization chemistry and instrumentation contributed to achieving baseline separation and accurate detection of trace levels of proteinogenic amino acids stereoisomers in different matrices. However, liquid and gas chromatography coupled to mass spectrometry based analytical methods remain the most popular platform in chiral amino acid analysis in terms of feasibility and performance. This review discusses different physicochemical and biological features and functions of proteinogenic amino acid stereoisomers and lists a variety of established chromatography and mass spectrometry based analytical methods for their analysis reported to date.

氨基酸(AAs)是重要的生物分子，在原核和真核生物系统中都具有多种功能。有22种天然氨基酸，其中20种常见的氨基酸出现在遗传密码中，被称为蛋白质生成氨基酸，它们是蛋白质的组成部分。蛋白质原氨基酸以两种异构体形式存在(甘氨酸除外)，其生物活性通常归因于特定的立体异构体。蛋白质中发现的大多数氨基酸主要是l - aa。少量的d -氨基酸存在于细菌细胞壁、一些海洋无脊椎动物和高等生物中，包括青蛙、蜗牛、蜘蛛、老鼠、鸡和人。除了它们在蛋白质合成中的作用外，不同的蛋白质生成氨基酸立体异构体已经被发现发挥重要的生物学作用，要么作为无数其他生物活性分子的前体，要么通过指示几种生物现象，即作为不同生理条件的标记。鉴于L-和d -氨基酸(AAs)的生物学重要性，改进的分析方法对它们的分辨率和准确定量仍然是人们关注的焦点。复杂生物基质中氨基酸的手性分析提出了许多分析挑战，这些挑战由于蛋白质原氨基酸立体异构体的极性和电离效率的巨大差异而加剧。迄今为止，报道了各种分析方法用于手性氨基酸分析，包括色谱，光谱，酶，流体，电泳和微生物技术。固定相、衍生化化学和仪器的进步有助于实现基线分离和准确检测不同基质中痕量的蛋白质原氨基酸立体异构体。然而，液相和气相色谱联用质谱分析方法在可行性和性能方面仍然是手性氨基酸分析中最流行的平台。本文综述了蛋白质氨基酸立体异构体的不同物理化学和生物学特征和功能，并列举了迄今为止报道的各种基于色谱和质谱的分析方法。

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引用次数: 15

Shigella pathogenesis: molecular and computational insights 志贺菌的发病机制：分子和计算见解

IF 1.4

AIMS Molecular Science

Pub Date : 2020-05-11 DOI: 10.3934/molsci.2020007

S. Mukhopadhyay, S. Ganguli, S. Chakrabarti

Shigellosis, characterized by inflammation and ulceration of the large intestine, is caused by infection with Shigella species. It is a major public health problem in developing countries where filthy sanitation practices and restricted access to clean water encourage the spread of the disease. Shigellosis is spread by means of fecal-oral route. It is one of the most common disorders specially affecting children in West Bengal, India. Disease from Shigella species accounts for 165 million cases of diarrhoea culminating in one million deaths annually worldwide. Severe dysentery is treated still with antibiotics, with limited success because of the continuous development of multi drug resistance by the bacteria. WHO has identified Shigella as a potential target pathogen against which new drugs need to be formulated and in silico approach has the potential to identify drug targets. Molecular modeling of Shigella invasion proteins using computational tools may divulge novel therapeutic targets that can be used for future pharmacological intervention. Detailed annotation of previously unknown Hypothetical Proteins using an in-silico pipeline can identify crucial proteins in pathogenesis cascade, which can be explored further as effective drug targets, which may eventually enable us to combat the menace of shigellosis.

志贺菌病以大肠炎症和溃疡为特征，是由志贺菌感染引起的。在发展中国家，这是一个主要的公共卫生问题，肮脏的卫生习惯和获得清洁水的限制助长了疾病的传播。志贺菌病通过粪口途径传播。它是最常见的疾病之一，特别影响到印度西孟加拉邦的儿童。志贺氏菌引起的腹泻病例达1.65亿例，全球每年有100万人死亡。严重痢疾仍使用抗生素治疗，但由于细菌对多种药物的耐药性不断发展，成功率有限。世界卫生组织已确定志贺氏菌是一种潜在的靶向病原体，需要配制新的药物，而硅方法有可能确定药物靶点。使用计算工具对志贺菌侵袭蛋白进行分子建模可能会揭示可用于未来药物干预的新治疗靶点。使用计算机管道对以前未知的假设蛋白质进行详细注释，可以确定发病机制级联中的关键蛋白质，这些蛋白质可以作为有效的药物靶点进一步探索，最终可能使我们能够对抗志贺菌病的威胁。

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引用次数: 2

Cell division symmetry control and cancer stem cells. 细胞分裂对称控制与癌症干细胞。

IF 1.4

AIMS Molecular Science

Pub Date : 2020-01-01 Epub Date: 2020-05-06 DOI: 10.3934/molsci.2020006

Sreemita Majumdar, Song-Tao Liu

Stem cells including cancer stem cells (CSC) divide symmetrically or asymmetrically. Usually symmetric cell division makes two daughter cells of the same fate, either as stem cells or more differentiated progenies; while asymmetric cell division (ACD) produces daughter cells of different fates. In this review, we first provide an overview of ACD, and then discuss more molecular details of ACD using the well-characterized Drosophila neuroblast system as an example. Aiming to explore the connections between cell heterogeneity in cancers and the critical need of ACD for self-renewal and generating cell diversity, we then examine how cell division symmetry control impacts common features associated with CSCs, including niche competition, cancer dormancy, drug resistance, epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET), and cancer stem cell plasticity. As CSC may underlie resistance to therapy and cancer metastasis, understanding how cell division mode is selected and executed in these cells will provide possible strategies to target CSC.

包括癌症干细胞(CSC)在内的干细胞分为对称分裂和不对称分裂。通常对称的细胞分裂会产生两个具有相同命运的子细胞，要么是干细胞，要么是分化程度更高的后代;而不对称细胞分裂(ACD)产生不同命运的子细胞。在这篇综述中，我们首先介绍了ACD的概况，然后以果蝇神经母细胞系统为例讨论了ACD的更多分子细节。为了探索癌症细胞异质性与ACD自我更新和产生细胞多样性的关键需求之间的联系，我们随后研究了细胞分裂对称控制如何影响与CSCs相关的常见特征，包括生态位竞争、癌症休眠、耐药性、上皮-间充质转化(EMT)及其反向过程间充质-上皮转化(MET)和癌症干细胞可塑性。由于CSC可能是抵抗治疗和癌症转移的基础，了解这些细胞如何选择和执行细胞分裂模式将为靶向CSC提供可能的策略。

引用次数: 13

Phospholipid synthetic and turnover pathways elicited upon exposure to different xenobiotics 磷脂的合成和转换途径引起的暴露于不同的外源性

IF 1.4

AIMS Molecular Science

Pub Date : 2020-01-01 DOI: 10.3934/molsci.2020010

Teresa M. Fonovich

Phospholipids, neutral lipids and glycolipids metabolism take the place during cell responses to different stimuli. Phospholipase and acyl glycerol lipase activities have been demonstrated to release second messengers that trigger cascade responses. Studies on lipid droplets structure, formation and interaction with other organelles have recently been described in prokaryotes and eukaryotes. Remodeling of membrane phospholipids has also been reported. NMR studies performed on synthetic membranes allowed to postulate membrane lipids polymorphism and to explain how processes like cell division, endocytosis and exocytosis can take place, due to special arrangements of the membranes. Studies from our research group on the pesticide dieldrin and Cu2+ effects through exposure of amphibian oocytes and embryos to sub-lethal and acclimation concentrations followed by toxic concentration challenges respectively, are discussed. Membrane phospholipids structure alterations allowing stabilization of bilayer arrangements were found for both stressors in cell and tissues. Metallothionein induction response that prevents oxidative stress was also found in acclimated embryo tissues. Probable connections between enzyme activities taking place on lysophospholipid and triacylglycerol substrates present in lipid droplets as well as phospholipid trafficking leading to modifications on membrane phospholipid ratios are discussed. Current new evidences in agreement with our findings allow us to suggest that our previously published results of dieldrin effects on amphibian cells correspond to joint coordinated activities, which probably had involved various metabolic pathways, in line with the acclimation experiment results and discussion. Independently of the cascade responses each toxicant is able to elicit, lipids play an important role in cell responses, both through rapid turnover and final stabilization of membrane bilayers.

磷脂、中性脂和糖脂代谢发生在细胞对不同刺激的反应过程中。磷脂酶和酰基甘油脂肪酶的活性已被证明可以释放触发级联反应的第二信使。最近在原核生物和真核生物中对脂滴的结构、形成和与其他细胞器的相互作用进行了研究。膜磷脂的重塑也有报道。在合成膜上进行的核磁共振研究允许假设膜脂多态性，并解释由于膜的特殊安排，细胞分裂，内吞作用和胞吐作用等过程如何发生。本文讨论了本课题组通过将两栖动物卵母细胞和胚胎分别暴露于亚致死浓度和驯化浓度以及毒性浓度挑战中对农药狄氏剂和Cu2+的影响。细胞膜磷脂结构的改变使得细胞和组织中的应激源的双层排列稳定。在驯化的胚胎组织中也发现了金属硫蛋白的诱导反应，以防止氧化应激。在脂滴中存在的溶血磷脂和三酰甘油底物上发生的酶活性之间的可能联系以及导致膜磷脂比率修饰的磷脂运输。目前的新证据与我们的研究结果一致，使我们认为我们之前发表的狄氏剂对两栖动物细胞的作用对应于联合协调的活动，可能涉及多种代谢途径，与驯化实验结果和讨论一致。独立于每种毒物能够引起的级联反应，脂质在细胞反应中发挥重要作用，通过快速周转和最终稳定膜双分子层。

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引用次数: 0

Nuclear neurotransmitter molecular imaging of autism spectrum disorder 自闭症谱系障碍的核神经递质分子成像

IF 1.4

AIMS Molecular Science

Pub Date : 2019-12-02 DOI: 10.3934/molsci.2019.4.87

A. Syed, James Robert Brašić

Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by marked deficits in social communication and interaction, including limited and repetitive patterns of behavior. We selected key nuclear neurotransmitter molecular imaging reports of ASD by combining “autism” AND “positron” AND “dopamine” OR “serotonin” OR “glutamate” OR “GABA” utilizing databases as follows: PubMed, Scopus, Web of Science, Science Direct, and Google Scholar. This review reports important findings in ASD utilizing positron emission tomography (PET) and single-photon emission computed tomography (SPECT). We studied major neurotransmitter systems, dopamine, serotonin, glutamate, and gamma-aminobutyric acid (GABA). Dopamine neurotransmission was decreased in the anterior medial prefrontal cortex in children with autism. Dopamine transporter was increased in the orbital frontal cortex of adults with ASD and decreased in the striatum of children with ASD. Decreased tryptophan metabolism, an estimate of serotonin synthesis, (A) in left frontal cortex correlated with severe language impairment and (B) in the right frontal cortex correlated with left and mixed handedness. Although not confirmed by some investigators, serotonin transporter was decreased in the cingulate, the medial frontal cortex, the midbrain, and the temporal lobes. Serotonin receptors were decreased in the thalamus in individuals with ASD and in the cortices of parents of children with ASD. Metabotropic glutamate receptor subtype 5 (mGluR 5 ) was increased in the post-central gyrus and the cerebellum of men with autism. PET studies for GABA did not differentiate people with ASD from controls. The increasing incidence of ASD and the inconsistent findings of different nuclear molecular imaging studies are evidence for the urgent need for further investigations utilizing nuclear molecular imaging to identify the key neurophysiological mechanisms underlying the pathophysiology of ASD.

自闭症谱系障碍(ASD)是一组发育障碍，其特征是社会沟通和互动的明显缺陷，包括有限和重复的行为模式。我们结合“自闭症”、“正电子”、“多巴胺”、“血清素”、“谷氨酸”或“GABA”等词，选取了与ASD相关的关键核神经递质分子成像报告，数据库包括PubMed、Scopus、Web of Science、Science Direct和谷歌Scholar。本文综述了利用正电子发射断层扫描(PET)和单光子发射计算机断层扫描(SPECT)在ASD中的重要发现。我们研究了主要的神经递质系统，多巴胺、血清素、谷氨酸和γ -氨基丁酸(GABA)。自闭症儿童前额叶前部内侧皮层多巴胺神经传递减少。多巴胺转运体在成人ASD患者眶额皮质中增加，在儿童ASD患者纹状体中减少。色氨酸代谢减少，估计5 -羟色胺合成，(A)在左额叶皮层与严重的语言障碍有关，(B)在右额叶皮层与左右手和混合型惯用手有关。虽然没有得到一些研究者的证实，但5 -羟色胺转运体在扣带回、内侧额叶皮层、中脑和颞叶中有所减少。5 -羟色胺受体在自闭症患者的丘脑和自闭症儿童父母的大脑皮层中减少。自闭症男性中脑后回和小脑的代谢性谷氨酸受体亚型5 (mGluR 5)增加。GABA的PET研究并没有将ASD患者与对照组区分开来。ASD发病率的增加和不同核分子成像研究结果的不一致，表明迫切需要进一步研究利用核分子成像来确定ASD病理生理背后的关键神经生理机制。

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引用次数: 2

Is there a role for melatonin in fibromyalgia? 褪黑素在纤维肌痛中有作用吗?

IF 1.4

AIMS Molecular Science

Pub Date : 2019-11-25 DOI: 10.3934/molsci.2019.4.73

K. Lawson

Fibromyalgia, characterised by persistent pain, fatigue, sleep disturbance and cognitive dysfunction, is a central sensitivity syndrome that also involves abnormality in peripheral generators and in the hypothalamic pituitary adrenal axis. Heterogeneity of clinical expression of fibromyalgia with a multifactorial aetiology has made the development of effective therapeutic strategies challenging. Physiological properties of the neurohormone melatonin appear related to the symptom profile exhibited by patients with fibromyalgia and thus disturbance of it’s production would be compatible with the pathophysiology. Altered levels of melatonin have been observed in patients with fibromyalgia which are associated with lower secretion during dark hours and higher secretion during daytime. However, inconsistencies of available clinical evidence limit conclusion of a relationship between levels of melatonin and symptom profiles in patients with fibromyalgia. Administration of melatonin to patients with fibromyalgia has demonstrated suppression of many symptoms and an improved quality of life consistent with benefit as a therapy for the management of this condition. Further studies with larger samples, however, are required to explore the potential role of melatonin in the pathophysiology of fibromyalgia and determine the optimal dosing regimen of melatonin for the management of fibromyalgia.

纤维肌痛以持续疼痛、疲劳、睡眠障碍和认知功能障碍为特征，是一种中枢敏感性综合征，也涉及外周发生器和下丘脑-垂体-肾上腺轴的异常。纤维肌痛临床表达的异质性与多因素病因使制定有效的治疗策略具有挑战性。神经激素褪黑素的生理特性似乎与纤维肌痛患者表现出的症状有关，因此其产生的紊乱与病理生理学是一致的。在纤维肌痛患者中观察到褪黑激素水平的变化，这与天黑时分泌量较低和白天分泌量较高有关。然而，现有临床证据的不一致性限制了纤维肌痛患者褪黑素水平与症状之间关系的结论。纤维肌痛患者服用褪黑激素已证明可以抑制许多症状，并提高生活质量，这与治疗纤维肌痛的益处一致。然而，需要对更大样本进行进一步研究，以探索褪黑素在纤维肌痛病理生理学中的潜在作用，并确定褪黑素治疗纤维肌痛的最佳给药方案。

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引用次数: 1

Autism-modifying therapy based on the promotion of a brain enzyme: An introductory case-report 基于促进脑酶的自闭症修饰疗法:一个介绍性病例报告

IF 1.4

AIMS Molecular Science

Pub Date : 2019-09-17 DOI: 10.3934/molsci.2019.3.52

D. Béroule

An interdisciplinary study of autism led to implicate the relatively poor degradation of synaptic serotonin , a molecule involved in brain development. Consequent metabolic imbalance of monoamine neurotransmitters is assumed to impede memory encoding across sleep stages, hence the building of aberrant neural structures linked with autistic symptoms. A medication can be derived from this theoretical approach, with the aim of regulating neuromodulation whereby proper neural networks may start growing over impaired ones. The Valproate anticonvulsant has been prescribed here for its contribution to the promotion of a relevant brain enzyme known as Monoamine oxidase A (MAOA). Whereas case-studies usually focus on a subset of symptoms for less than three months in mild to moderate autism, the evolution of every autistic symptom has been witnessed across one year in an 11-year boy with severe autism. Rapid improvement of sleep, followed by the rising of visual exploration, preceded positive shifts of the core symptoms noticeable nine months later, however still impeded by bursts of hyperactivity. The adjunctive medication of Methylphenidate psychostimulant permitted afterwards to increase the attention span without interfering with Valproate. Such combination of MAOA-inducer and psychostimulant eventually favored the gradual acquisition of social conditioning, without fully erasing poor habits issued from ten years of autism. Because restricted to a disease-modifying action, this dual therapy relies on accompanying educational assistance, as notably learnt from its exploratory monitoring. Other insights focus on specific biomarkers as well as functional polymorphisms of relevant genes promoters, with the aim of guiding future clinical trials.

一项关于自闭症的跨学科研究表明，突触血清素(一种与大脑发育有关的分子)的降解相对较差。由此产生的单胺类神经递质代谢失衡被认为会阻碍睡眠阶段的记忆编码，从而导致与自闭症症状相关的异常神经结构的形成。从这种理论方法中可以衍生出一种药物，其目的是调节神经调节，从而使正常的神经网络开始在受损的神经网络上生长。丙戊酸抗惊厥药在这里的作用是促进一种相关的脑酶，即单胺氧化酶a (MAOA)。虽然个案研究通常集中在轻度到中度自闭症中不到三个月的症状子集，但在一个患有严重自闭症的11岁男孩身上，每一种自闭症症状的演变都被见证了一年。9个月后，随着睡眠的快速改善，视觉探索能力的增强，核心症状出现了明显的积极变化，但仍然受到多动发作的阻碍。在不干扰丙戊酸的情况下，服用哌醋甲酯精神兴奋剂可以增加注意力的持续时间。这种maoa诱导剂和精神兴奋剂的组合最终有利于社会条件的逐渐获得，但没有完全消除10年自闭症形成的不良习惯。由于仅限于改善疾病的作用，这种双重治疗依赖于伴随的教育援助，特别是从其探索性监测中了解到。其他见解侧重于特定的生物标志物以及相关基因启动子的功能多态性，旨在指导未来的临床试验。

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引用次数: 2