An Exploration of the Transformation of the 8-Oxo-7,8-Dihydroguanine Radical Cation to Protonated 2-Amino-5-Hydroxy-7,9-Dihydropurine-6,8-Dione in a Base Pair.

A theoretical investigation was performed to disclose the transformation mechanism of 8-oxo-7,8-dihydroguanine radical cation (8-oxoG⋅+ ) to protonated 2-amino-5-hydroxy-7,9-dihydropurine-6,8-dione (5-OH-8-oxoG) in base pair. The energy profiles for three possible pathways of the events were mapped. It is shown that direct loss of H7 from base paired 8-oxoG⋅+ is the only energetically favorable pathway to generate neutral radical, 8-oxoG(-H7)⋅. Further oxidation of 8-oxoG(-H7)⋅ : C to 8-oxoG(-H7)+ : C is exothermic. However, the 8-oxoG(-H7)+ : C deprotonation from all possible active sites is infeasible, indicating the inaccessible second proton loss and the lack of essential intermediate 2-amino-7,9-dihydropurine-6,8-dione (8-oxoGOX ). This makes 8-oxoG(-H7)+ act as the precursor of hydration leading to the generation of protonated 5-HO-8-oxoG by stepwise fashion in base pair, which would initiate the step down guanidinohydantoin (Gh) pathway. These results clearly specify the structure-dependent transformation for 8-oxoG⋅+ and verify the emergence of protonated 5-HO-8-oxoG in base pair.

Bioinformatics analysis identifies the protective targets of omentin in mice with focal cerebral ischemia injury.

Omentin is known to play a protective role in ischemic stroke. However, its regulatory networks and downstream targets in the pathogenesis of IS are incompletely revealed now. In this study, the model of photochemical brain ischemia was constructed after omentin over-expression. 8 key differentially expressed genes (DEGs) were obtained and analyzed by transcriptome analysis. These DEGs were mainly related to the negative regulation of hormone secretion, cellular phosphate ion homeostasis, and other pathways. Moreover, the mRNA expression of predicted gene 3435 (Gm3435), ankyrin repeat domain 53 (Ankrd53), fibroblast growth factor 23 (Fgf23) and the Fgf23 protein expression were down-regulated after omentin over-expression in HT22 cells injured by oxygen-glucose deprivation (OGD). In conclusion, our findings identified 8 key DEGs regulated by omentin after IS. In vitro models, the Gm3435, Ankrd53, Fgf23 mRNA expression and the Fgf23 protein expression were further verified to consistent with the transcriptomics results.

Rational design of DNA platonic polyhedra with the minimal components number from topological perspective.

DNA has been considered an ideal raw material to build nanostructures. However, the majority of known DNA branched polyhedra are composed of multiple components. In this research, we propose a rational approach to design and analyze DNA Platonic branched polyhedra with two components according to the topological view. The results show that the fragments number and the strand configurations give a great impact on the minimal number of components. Insights from our research can provide practical benefits for the design and synthesis of DNA polyhedra or other highly complex polyhedral structures in labs.

A potential relationship between MMP-9 rs2250889 and ischemic stroke susceptibility.

Purpose: Ischemic stroke (IS), a serious cerebrovascular disease, greatly affects people's health and life. Genetic factors are indispensable for the occurrence of IS. As a biomarker for IS, the MMP-9 gene is widely involved in the pathophysiological process of IS. This study attempts to find out the relationship between MMP-9 polymorphisms and IS susceptibility. Methods: A total of 700 IS patients and 700 healthy controls were recruited. The single nucleotide polymorphism (SNP) markers of the MMP-9 gene were genotyped by the MassARRAY analyzer. Multifactor dimensionality reduction (MDR) was applied to generate SNP-SNP interaction. Furthermore, the relationship between genetic variations (allele and genotype) of the MMP-9 gene and IS susceptibility was analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Results: Our results demonstrated that rs2250889 could significantly increase the susceptibility to IS in the codominant, dominant, overdominant, and log-additive models (p < 0.05). Further stratification analysis showed that compared with the control group, rs2250889 was associated with IS risk in different case groups (age, female, smoking, and non-drinking) (p < 0.05). Based on MDR analysis, rs2250889 was the best model for predicting IS risk (cross-validation consistency: 10/10, OR = 1.56 (1.26-1.94), p < 0.001). Conclusion: Our study preliminarily confirmed that SNP rs2250889 was significantly associated with susceptibility to IS.

Association of MMP3, MMP14, and MMP25 gene polymorphisms with cerebral stroke risk: a case-control study.

BACKGROUND: Cerebral stroke (CS) is the leading cause of death in China, and a complex disease caused by both alterable risk factors and genetic factors. This study intended to investigate the association of MMP3, MMP14, and MMP25 single nucleotide polymorphisms (SNPs) with CS risk in a Chinese Han population. METHODS: A total of 1,348 Han Chinese were recruited in this case-control study. Four candidate loci including rs520540 A/G and rs679620 T/C of MMP3, rs2236302 G/C of MMP14, and rs10431961 T/C of MMP25 were successfully screened. The correlation between the four SNPs and CS risk was assessed by logistic regression analysis. The results were analyzed by false-positive report probability (FPRP) for chance or significance. The interactions between four SNPs associated with CS risk were assessed by multifactor dimensionality reduction (MDR). RESULTS: rs520540 A/G and rs679620 C/T SNP in MMP3 were associated with risk of CS in allele, codominant, dominant and log-additive models. Ischemic stroke risk were significantly lower in carriers with rs520540-A allele and rs679620-T allele than those with G/G or C/C genotypes. However, rs520540-A allele and rs679620-T allele were associated with higher risk of hemorrhagic stroke. Stratified analysis showed that these two SNPs were associated with reduced risk of CS in aged < 55 years, non-smoking and non-drinking participants, and rs679620 SNP also reduced CS risk in male participants. The levels of uric acid, high-density lipoprotein cholesterol, and eosinophil were different among patients with different genotypes of rs520540 and rs679620. No statistically significant association was found between MMP14 rs2236302 G/C or MMP25 rs10431961 T/C with CS even after stratification by stroke subtypes, age, gender as well as smoking and drinking conditions in all the genetic models. CONCLUSION: MMP3 rs520540 A/G and rs679620 C/T polymorphisms were associated with CS risk in the Chinese Han population, which provides useful information for the prevention and diagnosis of CS.

Aptamers for Viral Detection and Inhibition.

Recent times have experienced more than ever the impact of viral infections in humans. Viral infections are known to cause diseases not only in humans but also in plants and animals. Here, we have compiled the literature review of aptamers selected and used for detection and inhibition of viral infections in all three categories: humans, animals, and plants. This review gives an in-depth introduction to aptamers, different types of aptamer selection (SELEX) methodologies, the benefits of using aptamers over commonly used antibody-based strategies, and the structural and functional mechanism of aptasensors for viral detection and therapy. The review is organized based on the different characterization and read-out tools used to detect virus-aptasensor interactions with a detailed index of existing virus-targeting aptamers. Along with addressing recent developments, we also discuss a way forward with aptamers for DNA nanotechnology-based detection and treatment of viral diseases. Overall, this review will serve as a comprehensive resource for aptamer-based strategies in viral diagnostics and treatment.

An approach to generate DNA polyhedral links of one/two strands.

Scientists can change programmed DNA strands to adjust edge length and vertex junction to control the 3D structures with precision space signatures. The number of strands plays an important role in sequence design, synthesis and constitutive property. However, the majority of DNA branched polyhedra comprise a number of single strands. Therefore, it is crucial to make the number of strands to be calculated as less as possible. DNA polyhedral links are regarded as ideal templates of DNA polyhedra. In this research, we introduce odd-half turn edges and pseudo-surrounded vertexes to build DNA polyhedral links and reduce the strands number of them to one or two. Compare to the known strategies, our strategy is well established to generate the DNA polyhedral links of one/two DNA strands easier and faster. All Platonic, pyramid and prism polyhedral links may provide candidates for DNA polyhedra synthesis.

Biotechnological and Therapeutic Applications of Natural Nucleic Acid Structural Motifs.

Genetic information and the blueprint of life are stored in the form of nucleic acids. The primary sequence of DNA, read from the canonical double helix, provides the code for RNA and protein synthesis. Yet these already-information-rich molecules have higher-order structures which play critical roles in transcription and translation. Uncovering the sequences, parameters, and conditions which govern the formation of these structural motifs has allowed researchers to study them and to utilize them in biotechnological and therapeutic applications in vitro and in vivo. This review covers both DNA and RNA structural motifs found naturally in biological systems including catalytic nucleic acids, non-coding RNA, aptamers, G-quadruplexes, i-motifs, and Holliday junctions. For each category, an overview of the structural characteristics, biological prevalence, and function will be discussed. The biotechnological and therapeutic applications of these structural motifs are highlighted. Future perspectives focus on the addition of proteins and unnatural modifications to enhance structural stability for greater applicability.

Evaluation of biosynthesis parameters, stability and biological activities of silver nanoparticles synthesized by Cornus Officinalis extract under 365 nm UV radiation.

Since silver nanoparticles (AgNPs) synthesized by using plant extracts revealed varied biological activities, the green synthesis of AgNPs has attracted considerable attention. Although the green synthesis of AgNPs have been accomplished by using the extracts of Cornus Officinalis, which is a traditional Chinese medicine and exhibits a wide spectrum of phytochemicals. The effects of biosynthesis parameters on reducing reaction, stability and more broad biological activities of so-prepared AgNPs did not been evaluated. In this paper, we firstly assessed the effects of UV radiation, pH, material proportion and radiation times on the green synthesis of AgNPs under 365 nm UV radiation by UV-visible spectrum and dynamic light scattering (DLS) analysis. The results showed that UV radiation could accelerate the formation of AgNPs and influence the average size below pH 7.0, and the size of so-prepared AgNPs were sensitive to the pH and material proportion, but no obvious changes to UV radiation times, offering a size-controlled synthetic method for AgNPs. The further X-ray diffraction (XRD), transmission electron microscopy (TEM) and DLS studies showed AgNPs synthesized at pH 7.0, extract: AgNO3 = 1 : 1 and after 4 h UV radiation were a face-centered cubic (fcc) structure and both spherical and polygonal in shape with average particle size of 64.5 ± 0.3 nm existed in a monodispersed form. Subsquently, the stability of AgNPs was analyzed by zeta potential (-24.8 mV) and the average size measurement after 30 days storage (63.3 ± 0.4 nm), revealing a high degree of stability. Lastly, the investigation of biological activities showed that the biosynthesized AgNPs had potent antioxidant activity, antimicrobial activity against both S. aureus and E. coli as well as anticancer activity against HCT116 and HepG2 cell lines but negligible cytotoxicity against SW620. And the internalization of biosynthesized AgNPs inside the bacterial cell was evaluated by flow cytometric analysis, where the SSC values have significant increase after treating with nanoparticles. These results confirmed that the biosynthesis parameters on the green synthesis of AgNPs by using Cornus Officinalis extract also played pivotal roles and so-prepared AgNPs would be useful for the development of new alternative antioxidant, antimicrobial and anticancer agents in biomedicine.