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利用荧光相关光谱技术分析精神分裂症患者游离 DNA 的浓度和粒径分布。

Analysis of the concentrations and size distributions of cell-free DNA in schizophrenia using fluorescence correlation spectroscopy.

机构信息

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, 200030, China.

College of life sciences, Anhui Normal University, Wuhu, 241000, China.

出版信息

Transl Psychiatry. 2018 May 22;8(1):104. doi: 10.1038/s41398-018-0153-3.

Abstract

Cell-free DNA (cfDNA), which is primarily released following cell death, has been described and developed to serve as an effective biomarker in autoimmune diseases which may share the pathogenesis with schizophrenia. In this study, we hypothesized and explored whether the concentrations and size distributions of cfDNA are abnormal in schizophrenia. A total of 65 patients with schizophrenia (SZ), 29 patients with mood disorders (MD) and 62 matched healthy controls (HC) were included in the study. Fluorescence correlation spectroscopy was used to assay the molar concentrations and size distributions of cfDNA. Fluorometric quantification and quantitative real-time PCR (qPCR) were performed to verify the results. The cfDNA levels were approximately two-fold higher in the SZ group ((29 ± 15) nM) than in the healthy controls ((15 ± 9) nM; P-value = 0.00062), but the levels in patients with MD were not significantly different from those in the healthy controls ((17 ± 10) nM; P-value = 0.343). According to the size distribution analysis, cfDNA in schizophrenia patients was composed of shorter DNA molecules and showed an apoptosis-like distribution pattern. Our study shows the elevated levels and short sizes of cfDNA in schizophrenia patients, which provide direct evidences supporting increased apoptotic activity in the disease. cfDNA may be developed to serve as an auxiliary diagnostic marker for the disease in the future.

摘要

无细胞游离 DNA(cfDNA)主要在细胞死亡后释放,已被描述并开发为自身免疫性疾病的有效生物标志物,这些疾病的发病机制可能与精神分裂症共享。在这项研究中,我们假设并探讨了 cfDNA 的浓度和大小分布是否在精神分裂症中异常。共纳入 65 例精神分裂症(SZ)患者、29 例心境障碍(MD)患者和 62 名匹配的健康对照(HC)。荧光相关光谱法用于测定 cfDNA 的摩尔浓度和大小分布。荧光定量和实时定量 PCR(qPCR)用于验证结果。SZ 组的 cfDNA 水平((29 ± 15) nM)大约是健康对照组的两倍((15 ± 9) nM;P 值 = 0.00062),但 MD 患者的水平与健康对照组无显著差异((17 ± 10) nM;P 值 = 0.343)。根据大小分布分析,精神分裂症患者的 cfDNA 由较短的 DNA 分子组成,并表现出类似凋亡的分布模式。我们的研究表明,精神分裂症患者的 cfDNA 水平升高且大小较短,这为该疾病中凋亡活性增加提供了直接证据。cfDNA 可能在未来被开发为该疾病的辅助诊断标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3a/5966419/bfdeb4bbe9cf/41398_2018_153_Fig1_HTML.jpg

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