[Gene editing technology and its recent progress in disease therapy].

Gene editing is a genetic manipulation technology which utilizes bacterial nucleases to accurately and efficiently modify DNA or RNA. Gene editing has broad applications in basic research, breeding, and drug screening, and it is gaining validity and applicability to the therapy of many diseases especially genetic-based disease. In this review, we summarize the development of gene editing technology, its different strategies and applications in the treatment of disease, and the research of gene editing therapy for genetic diseases (including base editor and epigenetic regulation) in the treatment of disorders and diseases of the blood system, liver, muscle and nervous system. Finally, we discuss the future development prospects of gene editing therapy.

Prioritizing candidate disease miRNAs by topological features in the miRNA target-dysregulated network: case study of prostate cancer.

Recently, microRNAs (miRNA), small noncoding RNAs, have taken center stage in the field of human molecular oncology. However, their roles in tumor biology remain largely unknown. According to the assumption that miRNAs implicated in a specific tumor phenotype will show aberrant regulation of their target genes, we introduce an approach based on the miRNA target-dysregulated network (MTDN) to prioritize novel disease miRNAs. Target genes have predicted binding sites for any miRNA. The MTDN is constructed by combining computational target prediction with miRNA and mRNA expression profiles in tumor and nontumor tissues. Application of the proposed method to prostate cancer reveals that known prostate cancer miRNAs are characterized by a greater number of dysregulations and coregulators and the tendency to coregulate with each other and that they share a higher proportion of targets with other prostate cancer miRNAs. Support vector machine classifier, based on these features and changes in miRNA expression, is constructed and gives an average overall prediction accuracy of 0.8872 in cross-validation tests. The classifier is then applied to miRNAs in the MTDN. Functions enriched by dysregulated targets of novel predicted miRNAs are closely associated with oncogenesis. In addition, predicted cancer miRNAs within families or from different families show combinatorial dysregulation of target genes, as revealed by analysis of the MTDN modular organization. Finally, 3 miRNA target regulations are verified to hold in prostate cancer cells by transfection assays. These results show that the network-centric method could prioritize novel disease miRNAs and model how oncogenic lesions are mediated by miRNAs, providing important insights into tumorigenesis.

MiRNA-miRNA synergistic network: construction via co-regulating functional modules and disease miRNA topological features.

Synergistic regulations among multiple microRNAs (miRNAs) are important to understand the mechanisms of complex post-transcriptional regulations in humans. Complex diseases are affected by several miRNAs rather than a single miRNA. So, it is a challenge to identify miRNA synergism and thereby further determine miRNA functions at a system-wide level and investigate disease miRNA features in the miRNA-miRNA synergistic network from a new view. Here, we constructed a miRNA-miRNA functional synergistic network (MFSN) via co-regulating functional modules that have three features: common targets of corresponding miRNA pairs, enriched in the same gene ontology category and close proximity in the protein interaction network. Predicted miRNA synergism is validated by significantly high co-expression of functional modules and significantly negative regulation to functional modules. We found that the MFSN exhibits a scale free, small world and modular architecture. Furthermore, the topological features of disease miRNAs in the MFSN are distinct from non-disease miRNAs. They have more synergism, indicating their higher complexity of functions and are the global central cores of the MFSN. In addition, miRNAs associated with the same disease are close to each other. The structure of the MFSN and the features of disease miRNAs are validated to be robust using different miRNA target data sets.

[A study on the mathematical model of normal adult cornea].

OBJECTIVE: To explore the method on the conic equation to establish the mathematical model of the adult cornea and its preliminary result. METHODS: The curvature of anterior cornea and of posterior cornea, the corneal thickness of the points in the distance of 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5 mm away from the apex in the meridians of 0 degrees , 30 degrees , 60 degrees , 90 degrees , 120 degrees , 150 degrees , 180 degrees , 210 degrees , 240 degrees , 270 degrees , 300 degrees , 330 degrees meridians were collected from the Orbscan II topography. Cartesian coordinate was established with the origin at the apex of cornea and its horizontal, vertical and optical axes were defined as axis of X, Y and Z respectively. Then every point was located. The coordinate was circumrotated to establish a new coordinates to relocate the data of the points at the oblique meridians. The mathematical formulas of the meridians sections of the anterior and posterior surface were analyzed as: anterior surface: x2 = a1z2 + a2z, posterior surface: x2 = a1 (z-d0)2 + a2 (z-d0) (d0 is the corneal thickness). And the asphericity Q could be deduced. The mathematical formulas of the anterior and the posterior cornea surface as: anterior surface: x2 a2 + y2 b2 + (z-c)2 c2 = 1, posterior surface: x2 a2 + y2 b2 + (z-c-d0)2 c2 = 1. RESULTS: The mathematical models of the meridian section of the anterior and posterior surface of the cornea show conic formula as ellipse. The mathematical formulas of the anterior and the posterior cornea surface show conic surfaces. CONCLUSIONS: The paper reported a new method in conic formula to establish the mathematical model of the normal cornea. The shape of the meridians sections of the anterior and posterior surface of cornea are ellipse. The shape of the anterior and the posterior corneal surface are both ellipsoid.

[A study on the space form of the Schematic cornea of the normal adult eye-ball].

OBJECTIVE: To detect the initial characters of the corneal shape that has been evaluated using a mathematical analysis. METHODS: Subjects were measured with Orbscan II corneal topography system. Anterior and posterior corneal radius of curvature and thickness of the points located 1.5 mm, 2.5 mm, 3.5 mm and 4.5 mm away from the corneal apex on certain meridians, including 0 degrees , 30 degrees , 60 degrees , 90 degrees , 120 degrees , 150 degrees , 180 degrees , 210 degrees , 240 degrees , 270 degrees , 300 degrees and 330 degrees meridians, were measured. The mathematical formula of space-form of the cornea as well as the shape factor (SF) were demonstrated. Distributions of corneal curvature between the two principal meridians were discussed. RESULTS: Mathematical model of anterior and posterior corneal surface were small ha, Cyrillic(2)/8.053(2) + y(2)/7.973(2) + (z-8.226)(2)/8.226(2) = 1, x2/6.836(2) + y2/6.745(2) + (z-8.080)(2)/7.527(2) = 1 respectively. The SF models of the steepest and flattest meridians on anterior corneal surface were e(2) = 1-(15.61z-y2)/z2 and e2 = 1-(15.61 z-x2)/z2 respectively; the same parameters in the posterior corneal surface were e(2) = 1-[12.254 (z-0.553)-y2]/(z-0.553)(2) and e(2) = 1-[12.254 (z-0.553)-x2]/(z-0.553)(2) respectively. The curvature of oblique meridian was described with the formula F' = F(a) + (F(b)-F(a)).Sin(2)alpha. CONCLUSIONS: Anterior and posterior corneal surfaces are both toric similar to ellipsoidal. The distributions of corneal curvature between the two principal meridians have something to do with the law of Sine.