Alterations in factors associated with diabetic retinopathy combined with thrombosis: A review.

Diabetic retinopathy (DR) is one of the most common and serious microvascular complications of diabetes mellitus, the incidence of which has been increasing annually, and it is the main cause of vision loss in diabetic patients and a common cause of blindness. It is now found that thrombosis plays a crucial role in the disease progression in DR patients, and the final vision loss in DR may be related to the occurrence of thrombosis in the retinal vessels, which is dominated by abnormal endothelial cell function, together with platelet dysfunction, imbalance of coagulation and fibrinolytic function, and related alterations of inflammatory factors leading to the main cause of thrombotic disease in DR patients. In this review, we examine the role between DR and thrombosis and the association of each factor, including endothelial dysfunction; platelet dysfunction; coagulation-fibrinolytic imbalance; and alterations in inflammatory factors.

Ticlopidine induces cardiotoxicity in zebrafish embryos through AHR-mediated oxidative stress signaling pathway.

Ticlopidine has inhibitory effects on platelet aggregation via ADP (adenosine diphosphate), platelet release reaction and depolymerization. In clinical practice, it is commonly used to prevent heart, cerebrovascular and other thromboembolic diseases. However, ticlopidine has also been reported to have teratogenic effects on the heart, though its specific molecular mechanism remains unclear. In this study, zebrafish embryos were used as model organisms to examine the toxicity effect of ticlopidine. Zebrafish embryos exposed to 6, 7.5, and 9 mg/L ticlopidine solutions manifested several abnormalities, including body curvature, smaller eyes, slower absorption of the vitella sac, pericardial edema, slower heart rate, increased mortality, longer venous sinus - arterial ball (SV-BA) distance, and increased oxidative stress, which indicated developmental and cardiac toxicity. Abnormal expression of key genes related to heart development was observed, and the level of apoptotic gene expression was up-regulated. Further experiments revealed up-regulation of embryonic oxidative stress following ticlopidine exposure, leading to a decrease in cardiomyocyte proliferation. Conversely, the aromatic hydrocarbon receptor (AHR) inhibitor CH223191 protected embryos from the cardiotoxicity effect of ticlopidine, confirming further the role of up-regulated oxidative stress as the molecular mechanism of ticlopidine-induced cardiotoxicity in zebrafish. In conclusion, ticlopidine exposure leads to developmental and cardiotoxicity in zebrafish embryos. Therefore, further studies are warranted to ascertain such potential harms of ticlopidine in humans, which are vital in providing guidance in the safe use of drugs in clinical practice.

Photosynthetic Performance of Rice Seedlings Originated from Seeds Exposed to Spaceflight Conditions.

The mechanism of the regulation on photosynthesis after spaceflight has not been fully understood. To learn more information about this, we conducted a series of experiments of photosystem, including photosynthetic physiological characteristics (fluorescence parameters, pigment contents), gene expression and proteomic change. We want to examine the response of rice (Oryza sativaDN416), whose seeds were placed in Bio-Radiation Box on the ShiJian-10(SJ-10) recoverable satellite. Our results demonstrated that the photosynthesis capacity of plants after spaceflight declined, compared to ground control plants. Specifically, Fv/Fm is significantly reduced for 7.5%. Chlorophyll content decreased in the three growth stages of rice, trefoil, tillering and mature stages. To further analyze changes under spaceflight environment, quantitative real-time PCR technology and isobaric tags for relative and absolute quantization (iTRAQ) labeling technology were deployed. We found that the gene expression of important subunits of key enzymes and important structures had been decreased after spaceflight. As for the results of changes in proteins, we discovered that the content of proteins related to electron transport and photosynthesis key enzyme declined. Our experiments can provide reference for further research to learn more about the effects of spaceflight on photosynthesis.

Direct Demonstration of DNA Compaction Mediated by Divalent Counterions.

We unambiguously demonstrated DNA attraction and its regulation mediated by divalent cations Mg2+ and Ca2+ by tethering a DNA single chain at various pH solutions. It is found that DNA is compacted when the pH of the solution containing these divalent counterions is decreased below 5. When the pH of the medium is ∼4, DNA is in an unstable transition state, being able to switch between compact and extensible states. We can also regulate the DNA attraction through a cyclic process of DNA compaction and unraveling by alternating the pH of the solution between 3 and 8. The corresponding change of morphology of DNA modulated by pH is also confirmed by atomic force microscopy (AFM). In the theoretical aspect, the present experimental finding is consistent with the coarse-grained simulation of Langevin dynamics on the effect of pH on DNA in a solution of divalent counterions.

Tauroursodeoxycholic acid inhibits TNF-α-induced lipolysis in 3T3-L1 adipocytes via the IRE-JNK-perilipin-A signaling pathway.

The present study investigated the effects of tauroursodeoxycholic acid (TUDCA) on the lipolytic action of tumor necrosis factor (TNF)-α in 3T3-L1 adipocytes. Following treatment with TNF­α, cell viability was determined by MTT assay to select the optimum concentration and duration of TNF­α treatment in 3T3­L1 adipocytes. Intracellular lipid droplet dispersion and glycerin content in culture media were determined to evaluate the effect of TUDCA on TNF­α­induced lipolysis in 3T3­L1 adipocytes. Western blotting was performed to detect protein expression levels of perilipin­A and protein markers of endoplasmic reticulum stress: Immunoglobulin­binding protein (BiP), inositol­requiring enzyme (IRE), c­Jun N­terminal kinase (JNK), phosphorylated (p)­IRE and p­JNK. Following treatment with 50 ng/ml TNF­α for 24 h, glycerin content increased significantly and lipid droplets were dispersed. Glycerin content was reduced significantly and dispersal of lipid droplets reduced following pretreatment of 3T3­L1 adipocytes with 1 mmol/l TUDCA. TNF­α additionally activated the expression of BiP, p­IRE and p­JNK in a time­dependent manner; following pretreatment of 3T3­L1 adipocytes with 1 mmol/l TUDCA, the expression levels of these three proteins decreased. Therefore, TUDCA may inhibit TNF-α-induced lipolysis in 3T3­L1 adipocytes and reduce production of free fatty acids. Its underlying molecular mechanisms are potentially associated with the inhibition of activation of the IRE­JNK signaling pathway, which influences perilipin-A expression levels.

DNA Compaction and Charge Inversion Induced by Organic Monovalent Ions.

DNA condensation and charge inversion usually occur in solutions of multivalent counterions. In the present study, we show that the organic monovalent ions of tetraphenyl chloride arsenic (Ph4As⁺) can induce DNA compaction and even invert its electrophoretic mobility by single molecular methods. The morphology of condensed DNA was directly observed by atomic force microscopy (AFM) in the presence of a low concentration of Ph4As⁺ in DNA solution. The magnetic tweezers (MT) measurements showed that DNA compaction happens at very low Ph4As⁺ concentration (≤1 µM), and the typical step-like structures could be found in the extension-time curves of tethering DNA. However, when the concentration of Ph4As⁺ increased to 1 mM, the steps disappeared in the pulling curves and globular structures could be found in the corresponding AFM images. Electrophoretic mobility measurement showed that charge inversion of DNA induced by the monovalent ions happened at 1.6 mM Ph4As⁺, which is consistent with the prediction based on the strong hydrophobicity of Ph4As⁺. We infer that the hydrophobic effect is the main driving force of DNA charge inversion and compaction by the organic monovalent ion.