Multiomics and blood-based biomarkers of moyamoya disease: protocol of Moyamoya Omics Atlas (MOYAOMICS)
Peicong GeZihan YinChuming TaoChaofan ZengXiaofan YuShixiong LeiJunsheng LiYuanren ZhaiLong MaQiheng HeChenglong LiuWei LiuBojian ZhangZhiyao ZhengSiqi MouZhikang ZhaoShuang WangWei SunMin GuoShuai ZhengJia ZhangXiaofeng DengXingju LiuXun YeQian ZhangRong WangYan ZhangShaosen ZhangChengjun WangZiwen YangNijia ZhangMingxing WuJian SunYujia ZhouZhiyong ShiYonggang MaJianpo ZhouShaochen YuJiaxi LiJunli LuFaliang GaoWenjing WangYanming ChenXingen ZhuDong ZhangJizong Zhao
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Abstract Background Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. Methods The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. Conclusions The MOYAOMICS project represents a significant step toward comprehending MMD’s molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.Keywords:
Moyamoya Disease
Omics
Moyamoya disease is a cerebrovascular disorder characterized by bilateral stenosis or occlusion of the terminal portions of the internal carotid arteries accompanied by typical net-like collateral vessels in the basal ganglia. Although the etiology of moyamoya disease remains unknown, hereditary and immunogenic as well as hemodynamic factors have been implicated in the underlying mechanism of moyamoya disease. We report two patients with confirmed moyamoya disease and a patient with probable moyamoya disease complicated with Graves' disease. We reviewed the literature and summarized 23 cases of moyamoya disease or probable moyamoya, coexisting with Graves' disease.
Moyamoya Disease
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Cerebrovascular disorder
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The term "omics" refers to any type of specific study that provides collective information on a biological system. Representative omics includes genomics, proteomics, and metabolomics, and new omics is constantly being added, such as lipidomics or glycomics. Each omics technique is crucial to the understanding of various biological systems and complements the information provided by the other approaches. The main strengths of metabolomics are that metabolites are closely related to the phenotypes of living organisms and provide information on biochemical activities by reflecting the substrates and products of cellular metabolism. The transcriptome does not always correlate with the proteome, and the translated proteome might not be functionally active. Therefore, their changes do not always result in phenotypic alterations. Unlike the genome or proteome, the metabolome is often called the molecular phenotype of living organisms and is easily translated into biological conditions and disease states. Here, we review the general strategies of mass spectrometry-based metabolomics. Targeted metabolome or lipidome analysis is discussed, as well as nontargeted approaches, with a brief explanation of the advantages and disadvantages of each platform. Biomedical applications that use mass spectrometry-based metabolomics are briefly introduced.
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Moyamoya disease (MMD) is characterized by progressive occlusion of the internal carotid artery or its terminal branches, associated with formation of extensive collateral vessels (moyamoya vessels) at the base of the brain. Whether unilateral moyamoya disease, confirmed by typical angiographic evidence of moyamoya disease unilaterally and normal or equivocal findings contralaterally, is an early form of definite (bilateral) moyamoya disease remains controversial. Inherited or acquired disorders and conditions may present in conjunction with moyamoya disease. This condition is known as quasi-moyamoya disease (quasi-MMD). We attempted to determine the incidence and total patient number of moyamoya disease, unilateral MMD and quasi-MMD, who were treated during 2005 in Japan. Questionnaires were sent to 2,998 departments, which are listed in resident training programs of neurosurgery, neurology and pediatrics. Totally, 1,183 departments replied, and the response rate was 39.5%. The number of annual first-visit patients of MMD, unilateral MMD and quasi-MMD is 571, 118, and 53, respectively. Thus, the number of annual revisit patients of MMD, unilateral MMD and quasi-MMD is 2,064, 214, and 117 respectively. It is estimated that 6,670.9 MMD patient exists in Japan. The incidence rate of MMD, unilateral MMD and quasi-MMD is 1.13, 0.23 and 0.11/100,000, respectively, and the prevalence is 5.22, 0.66 and 0.34/100,000, respectively. This nationwide study revealed the present epidemic status of MMD, unilateral MMD and quasi-MMD.
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Many serious adverse physiological changes occur during spaceflight. In the search for underlying mechanisms and possible new countermeasures, many experimental tools and methods have been developed to study microgravity caused physiological changes, ranging from in vitro bioreactor studies to spaceflight investigations. Recently, genomic and proteomic approaches have gained a lot of attention; after major scientific breakthroughs in the fields of genomics and proteomics, they are now widely accepted and used to understand biological processes. Understanding gene and/or protein expression is the key to unfolding the mechanisms behind microgravity-induced problems and, ultimately, finding effective countermeasures to spaceflight-induced alterations. Significant progress has been made in identifying the genes/proteins responsible for these changes. Although many of these genes and/or proteins were observed to be either upregulated or downregulated, however, no large-scale genomics and proteomics studies have been published so far. This review aims at summarizing the current status of microgravity-related genomics and proteomics studies and stimulating large-scale proteomics and genomics research activities.
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Metabolomics has been applied to measure the dynamic metabolic responses, to understand the systematic biological networks, to reveal the potential genetic architecture, etc., for human diseases and livestock traits. For example, the current published results include the detected relevant candidate metabolites, identified metabolic pathways, potential systematic networks, etc., for different cattle traits that can be applied for further metabolomic and integrated omics studies. Therefore, summarizing the applications of metabolomics for economic traits is required in cattle. We here provide a comprehensive review about metabolomic analysis and its integration with other omics in five aspects: (1) characterization of the metabolomic profile of cattle; (2) metabolomic applications in cattle; (3) integrated metabolomic analysis with other omics; (4) methods and tools in metabolomic analysis; and (5) further potentialities. The review aims to investigate the existing metabolomic studies by highlighting the results in cattle, integrated with other omics studies, to understand the metabolic mechanisms underlying the economic traits and to provide useful information for further research and practical breeding programs in cattle.
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Objective: To investigate the clinical efficacy of superficial temporal artery -middle cerebral artery combined with encephalo-duro-arterio-myo-synangiosis (STA-MCA+EDAMS) and encephalo-duro-arterio-myo-synangiosis (EDAMS) in the treatment of adult moyamoya disease. Methods: The clinical data of 47 adult patients with moyamoya disease who received vascular reconstruction in the Department of Neurosurgery of Taizhou Hospital of Zhejiang Province from January 2014 to January 2018 were retrospectively analyzed. Among them, 21 patients received EDAMS alone (EDAMS group, 14 patients with hemorrhagic moyamoya disease, 7 patients with ischemic moyamoya disease), 26 patients received STA-MCA combined with EDAMS (STA-MCA+EDAMS group, 17 patients with hemorrhagic moyamoya disease, 9 patients with ischemic moyamoya disease). Cerebral hemodynamics at 1 day before surgery and 3 and 6 months after surgery were compared. The clinical efficacy and postoperative complications of the two methods were compared at 3 and 6 months postoperatively in hemorrhagic and ischemic types. Results: For hemorrhagic moyamoya disease, the remission rate (94.1%) at 6 months after surgery in the STA-MCA + EDAMS group was higher than that in the EDAMS group (57.1%), and the difference was statistically significant (P<0.05). The CBF and CBV in the STA-MCA+EDAMS group were higher than those in the EDAMS group at 3 and 6 months after operation, and the MTT and TPP were lower than those in the EDAMS group, but there was no significant difference between the two groups (all P>0.05). For hemorrhagic moyamoya disease and ischemic moyamoya disease, the total incidence of postoperative complications of the two surgical methods was different, but the difference was not statistically significant (both P>0.05). Conclusion: Superficial temporal artery -middle cerebral artery combined with encephalo-duro- arterio-myo-synangiosis (STA-MCA+EDAMS) and encephalo-duro-arterio-myo-synangiosis (EDAMS) can significantly improve neurological function and cerebral hemodynamics in adult moyamoya disease patients with high safety.目的: 探讨颞浅动脉-大脑中动脉搭桥联合脑-硬膜-动脉-颞肌贴敷术(STA-MCA+EDAMS)以及脑-硬膜-动脉-颞肌贴敷术(EDAMS)治疗成人烟雾病的安全性和有效性。 方法: 回顾性分析2014年1月至2018年1月在浙江省台州医院神经外科接受血管重建术治疗的47例成人烟雾病患者的临床资料,其中接受单纯EDAMS者21例(EDAMS组),其中出血型烟雾病14例,缺血型烟雾病7例;接受STA-MCA联合EDAMS者26例(STA-MCA+EDAMS组),其中出血型烟雾病17例,缺血型烟雾病9例。比较2组术前1 d及术后3、6个月的脑血流动力学指标,按出血型和缺血型分别比较2种术式术后3、6个月的临床疗效及术后并发症情况。 结果: 出血型烟雾病中STA-MCA+EDAMS组术后6个月的缓解率为94.1%(16/17),EDAMS组为57.1%(8/14),差异有统计学意义(P<0.05)。STA-MCA+EDAMS组术后3、6个月的脑血流量、脑血容量高于EDAMS组,平均通过时间、达峰时间低于EDAMS组,但差异均无统计学意义(均P>0.05)。不管是出血型烟雾病还是缺血型烟雾病,两种术式术后总并发症发生率差异均无统计学意义(均P>0.05)。 结论: 颞浅动脉-大脑中动脉搭桥联合脑-硬膜-动脉-颞肌贴敷术以及脑-硬膜-动脉-颞肌贴敷术治疗成人烟雾病均可显著改善患者神经功能和脑血流动力学指标,安全性较高。.
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Cotton genome project is being implemented and functional genomics has already played an essential role in cotton research.Great molecular progress has been made in genomic and proteomic field of cotton recently.This paper reviewed the progress of the cotton genomic and proteomics,particularly focusing on its genetic map,physical map,functional genome,proteomic techniques and cotton proteomics.
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Gossypium
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An unverified disease called "Moyamoya Disease" or "Spontaneous occlusion of the circle of Willis" has been recently reported as a disease entity by some Japanese researchers. Since the first report of this disease by Shimizu and the author in 1955, many cases have been reported not only in Japan but in many countries outside Japan. It has been already clarified either clinically or pathologically, that, in the Moyamoya Disease, the most important finding is the basal arterial occlusive change of unknown etiology and the Moyamoya Phenomenon is only nonspecific neuroradiological change as the extraordinary dilated collaterals via the striate arteries, perforators etc. However, the real cause of the arterial obstruction is still obscure in the so-called "true Moyamoya Disease". Further studies will be necessary in order to establish a new clinical entity related to the Moyamoya Disease. However, under existing situations, the Moyamoya Disease must be strictly differentiated from the Moyamoya Phenomenon which can be frequently observed among cases with basal occlusion of known and unknown origin.
Moyamoya Disease
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Circle of Willis
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