帕金森氏病关联miRNAs的功能和调控

帕金森病（Parkinson's disease, PD）是一种老年期常见的神经系统退行性疾病,致病过程复杂,其发病机制尚未明确,目前普遍认为帕金森病的发生与环境、遗传和年龄等多个因素有关。microRNAs（miRNAs）是一种内源性的小分子非编码RNAs,在转录后水平调控人类基因组中约1/3的基因。大量研究表明,帕金森病与miRNAs存在密切关联,在PD的发生发展、诊断甚至治疗过程中起到重要作用。本综述讨论了最近研究报道的和帕金森病相关的miRNAs,并分析了miRNAs的特异性表达在帕金森病的致病机制和诊断中发挥的作用。     

Identification of Tumor Antigens in Ovarian Cancers Using Local and Circulating Tumor-Specific Antibodies

Ovarian cancers include several disease subtypes and patients often present with advanced metastatic disease and a poor prognosis. New biomarkers for early diagnosis and targeted therapy are, therefore, urgently required. This study uses antibodies produced locally in tumor-draining lymph nodes (ASC probes) of individual ovarian cancer patients to screen two separate protein microarray platforms and identify cognate tumor antigens. The resulting antigen profiles were unique for each individual cancer patient and were used to generate a 50-antigen custom microarray. Serum from a separate cohort of ovarian cancer patients encompassing four disease subtypes was screened on the custom array and we identified 28.8% of all ovarian cancers, with a higher sensitivity for mucinous (50.0%) and serous (40.0%) subtypes. Combining local and circulating antibodies with high-density protein microarrays can identify novel, patient-specific tumor-associated antigens that may have diagnostic, prognostic or therapeutic uses in ovarian cancer.     

Dopamine Transporter Imaging,Current Status of a Potential Biomarker: A Comprehensive Review

A major goal of current clinical research in Parkinson’s disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD pathophysiology, and demonstrating target engagement in clinical trials. Molecular imaging with specific dopamine-related tracers offers a practical indirect imaging biomarker of PD, serving as a powerful tool to assess the status of presynaptic nigrostriatal terminals. In this review we provide an update on the dopamine transporter (DAT) imaging in PD and translate recent findings to potentially valuable clinical practice applications. The role of DAT imaging as diagnostic, preclinical and predictive biomarker is discussed, especially in view of recent evidence questioning the incontrovertible correlation between striatal DAT binding and nigral cell or axon counts.     

Identification of VEGF Signaling Inhibition-Induced Glomerular Injury in Rats through Site-Specific Urinary Biomarkers

Cancer therapies targeting the vascular endothelial growth factor (VEGF) signaling pathway can lead to renal damage by disrupting the glomerular ultrafiltration apparatus. The objective of the current study was to identify sensitive biomarkers for VEGF inhibition-induced glomerular changes in rats. Male Sprague-Dawley rats were administered an experimental VEGF receptor (VEGFR) inhibitor, ABT-123, for seven days to investigate the correlation of several biomarkers with microscopic and ultrastructural changes. Glomeruli obtained by laser capture microdissection were also subjected to gene expression analysis to investigate the underlying molecular events of VEGFR inhibition in glomerulus. ABT-123 induced characteristic glomerular ultrastructural changes in rats, including fusion of podocyte foot processes, the presence of subendothelial electron-dense deposits, and swelling and loss of fenestrations in glomerular endothelium. The subtle morphological changes cannot be detected with light microscopy or by changes in standard clinical chemistry and urinalysis. However, urinary albumin increased 44-fold as early as Day three. Urinary β2-microglobulin levels were also increased. Other urinary biomarkers that are typically associated with tubular injury were not significantly impacted. Such patterns in urinary biomarkers can provide valuable diagnostic insight to VEGF inhibition therapy-induced glomeruli injuries.     

Gelatin controversies in food,pharmaceuticals, and personal care products: Authentication methods,current status,and future challenges

Gelatin is a highly purified animal protein of pig, cow, and fish origins and is extensively used in food, pharmaceuticals, and personal care products. However, the acceptability of gelatin products greatly depends on the animal sources of the gelatin. Porcine and bovine gelatins have attractive features but limited acceptance because of religious prohibitions and potential zoonotic threats, whereas fish gelatin is welcomed in all religions and cultures. Thus, source authentication is a must for gelatin products but it is greatly challenging due to the breakdown of both protein and DNA biomarkers in processed gelatins. Therefore, several methods have been proposed for gelatin identification, but a comprehensive and systematic document that includes all of the techniques does not exist. This up-to-date review addresses this research gap and presents, in an accessible format, the major gelatin source authentication techniques, which are primarily nucleic acid and protein based. Instead of presenting these methods in paragraph form which needs much attention in reading, the major methods are schematically depicted, and their comparative features are tabulated. Future technologies are forecasted, and challenges are outlined. Overall, this review paper has the merit to serve as a reference guide for the production and application of gelatin in academia and industry and will act as a platform for the development of improved methods for gelatin authentication.     

Unraveling the Relevance of ARL GTPases in Cutaneous Melanoma Prognosis through Integrated Bioinformatics Analysis

Cutaneous melanoma (CM) is the deadliest skin cancer, whose molecular pathways underlying its malignancy remain unclear. Therefore, new information to guide evidence-based clinical decisions is required. Adenosine diphosphate (ADP)-ribosylation factor-like (ARL) proteins are membrane trafficking regulators whose biological relevance in CM is undetermined. Here, we investigated ARL expression and its impact on CM prognosis and immune microenvironment through integrated bioinformatics analysis. Our study found that all 22 ARLs are differentially expressed in CM. Specifically, ARL1 and ARL11 are upregulated and ARL15 is downregulated regardless of mutational frequency or copy number variations. According to TCGA data, ARL1 and ARL15 represent independent prognostic factors in CM as well as ARL11 based on GEPIA and OncoLnc. To investigate the mechanisms by which ARL1 and ARL11 increase patient survival while ARL15 reduces it, we evaluated their correlation with the immune microenvironment. CD4⁺ T cells and neutrophil infiltrates are significantly increased by ARL1 expression. Furthermore, ARL11 expression was correlated with 17 out of 21 immune infiltrates, including CD8⁺ T cells and M2 macrophages, described as having anti-tumoral activity. Likewise, ARL11 is interconnected with ZAP70, ADAM17, and P2RX7, which are implicated in immune cell activation. Collectively, this study provides the first evidence that ARL1, ARL11, and ARL15 may influence CM progression, prognosis, and immune microenvironment remodeling.     

中生代-新生代大陆边缘盆地海相烃源岩成因类型

中生代-新生代大陆边缘盆地海相烃源岩虽沉积于海洋环境,但有机质生源输入复杂。海相烃源岩显微组分组成中不仅有代表低等水生生物输入的腐泥组分,而且有较多指示陆生高等植物成因的镜质组、惰质组或壳质组。烃源岩生物标志化合物的分布特征也呈现出有机质生源输入二元性的特点,具体表现在饱和烃正构烷烃的分布面貌以双峰态为主,部分呈单峰态。C₂₇-C₂₉规则甾烷的分布型式以不对称的"V"字型为主,部分呈"L"型或反"L"型分布;除指示水生生物输入的C₂₃三环萜烷外,代表陆源有机质输入的奥利烷、四环萜烷和其他低分子量的三环萜烷均有分布。中生代-新生代大陆边缘盆地海相烃源岩生源组成复杂,这一特殊现象是大陆边缘盆地海洋和大陆两种地质营力、低等水生生物和陆生高等植物双重生源输入共同作用的结果。根据生源构成可将中生代-新生代大陆边缘盆地海相烃源岩划分为3种成因类型,即以藻类生源输入为主的内源型、以高等植物输入为主的陆源型及介于两者之间的混合生源型,并进一步揭示海相烃源岩的成因类型与干酪根类型之间可以通过显微组分组成、有机元素组成以及生物标志化合物分布联系起来。     

Oil: Source rock correlations of Al Baraka oil field,Komombo basin,South Egypt: An implication from biomarkers characteristics

The objectives of this study are the correlation between the oil samples recovered from the Lower Cretaceous reservoirs and Lower and Upper Cretaceous source rocks. The investigated biomarkers of five oils indicated the oils were derived from mixed marine and terrigenous (lacustrine) organic matter and deposited under suboxic to anoxic conditions. These oils were also generated from source rocks of high thermal maturity at the peak oil window. So, based on the molecular indicators of organic source input,depositional environment and maturity parameters of oils and extracts, we can conclude that the oil recovered from Al Baraka oil field were derived from Lower Cretaceous source rocks especially KomOmbo (B) source rocks where it reached the oil window. Furthermore, we can indicate that the other lower Cretaceous formations as Abu Ballas Formation will have the opportunity to generate and expel oil at the deeper part of the basin as shown in the eastern part of the basin.     

Analytical authentication of organic products: an overview of markers

Consumers' interest in organic foods is increasing and so is the need for robust analytical tools for their authentication. This review focuses on the most promising biomarkers/analytical approaches that are available for the authentication of organic produce. Food products have been subdivided into two groups: foods of plant origin (crops) and foods of animal origin (meat, milk and dairy products, eggs and fish). For each food category the most suitable biomarkers are presented and their potential for authentication is discussed. In the light of current knowledge, it is unlikely that the authentication of organic food products can be attained by the measurement of a single marker. Analytical approaches based on the measurement of multiple markers and/or complex chemical or physical profiles/fingerprints supported by multivariate statistical analysis seem considerably more promising in this respect. For the development of robust classification models, well‐designed experimental studies must be performed that rely on data sets that are both well balanced and of sufficient size to ensure that all relevant sources of variation for the target biomarkers are included in the reference database. Copyright © 2012 Society of Chemical Industry