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Introduction/Aims: There are no blood biomarkers to monitor treatment effects in myasthenia gravis (MG) or studies visualizing the acetylcholine receptor (AChR) antibody‐induced membrane attack complex (MAC) at the human muscle membrane. This study aimed to compare levels of complement activation products and native complement components in MG patients and healthy controls (HCs) and to model the AChR antibody‐mediated attacks in human muscle cells. Methods: We assessed the complement components and activation product levels with enzyme‐linked immunosorbent assay and magnetic bead‐based sandwich assays in plasma and sera of 23 MG patients and matched HCs. Receiver operator characteristic (ROC) curve analysis evaluated the diagnostic accuracy. Complement levels were correlated with the myasthenia gravis composite (MGC) scores. AChR+ MG modeling in human muscle cells used sera from nine MG patients and three HCs. Results: MG patients had significantly higher plasma levels of C3a (p <.0001), C5 (p =.0003), and soluble C5b‐9 (sC5b‐9; p <.0001) than HCs. The ROC curve analysis showed a clear separation between MG patients and HCs for plasma C3a (AUC = 0.9720; p <.0001) and sC5b‐9 (AUC = 0.8917, p <.0001). MG patients had higher levels of plasma complement Factor I (FI; p =.0002) and lower properdin levels (p <.0001). The MGC had moderate correlations with plasma Factor B (FB), FI, and Factor H. AChR+ MG patient sera triggered the deposition of MAC and reduced AChRs. Discussion: We suggest validating plasma C3a and sC5b‐9 as blood biomarkers for complement activation in MG. Further, the in vitro study allowed visualization of MAC deposition after applying AChR+ MG sera on human muscle cells. [ABSTRACT FROM AUTHOR]

A computational model for logical reasoning is proposed based on DNA strand displacement reactions.Firstly,this way does not rely on fluorescent labeling or other DNA experimental technique.The corresponding relationship between the concentration change of DNA strand and the value of Boolean logic signal is realized by building up a special 0-1 function and using less DNA reaction strands and strand displacement reactions as possible as we can.Then the calculation models of basic logical operations "and" "or" "not" are designed based on DNA strand displacement.Furthermore,the basic logical operations can be combined arbitrarily in use of the cascading property of DNA strand displacement,so as to solve different logical reasoning problems.Finally,the feasible solution of satisfiability problem,which is a special logical reasoning problem,is implemented through the simulation.All the DNA strand displacement reaction processes and the concentration changes of related DNA chains can be simulated by the Visual DSD software.

Introduction/Aims: The circulating microRNAs (miRNAs) miR‐150‐5p, miR‐30e‐5p, and miR‐21‐5p have been suggested as potential biomarkers for myasthenia gravis (MG); however, the relationships between short‐term natural changes of the miRNAs and patient‐reported MG outcome scores have not been well‐studied. We assessed the short‐term fluctuations in miRNA levels and patient‐reported outcome measures in MG. Methods: This prospective cohort study included 39 MG patients with regular follow‐ups and unchanged medications at the Neurology outpatient clinic at Uppsala University Hospital. Patients had weekly follow‐up visits for 1 month, at which blood samples were drawn, and scores from MG activities of daily living (MG‐ADL), MG quality‐of‐life‐15 (MG‐QoL15), and Fatigue Severity Scale (FSS) were assessed. Serum levels of miRNA miR‐150‐5p, miR‐30e‐5p, and miR‐21‐5p were analyzed using quantitative real‐time PCR. Results: Intra‐individual levels of miR‐30e‐5p and miR‐150‐5p were stable, whereas a significant reduction in miR‐21‐5p was observed from week 1 to week 2 (p =.0024) and from week 2 to week 3 (p <.0001). There were intra‐individual differences over a short time in MG‐ADL, with higher scores in female patients (p =.0281) and a significant reduction from the first to the second weeks (p =.0281), whereas MG‐QoL15 and FSS scores were stable. Discussion: The suggested MG biomarkers miR‐30e‐5p and miR‐150‐5p were more stable than miR‐21‐5p over a short time, indicating their short‐term stability as biomarkers. Prospective multi‐center studies with longer periods of follow‐up and matched controls are needed to validate these miRNAs as biomarkers in MG. [ABSTRACT FROM AUTHOR]

Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy. [ABSTRACT FROM AUTHOR]