Altered synchronous neural activities in retinal vein occlusion patients: A resting-state fMRI study.

Objective: Retinal vein occlusion (RVO) is the second most common retinal vascular disorder after diabetic retinopathy, which is the main cause of vision loss. Retinal vein occlusion might lead to macular edema, causing severe vision loss. Previous neuroimaging studies of patients with RVO demonstrated that RVO was accompanied by cerebral changes, and was related to stroke. The purpose of the study is to investigate synchronous neural activity changes in patients with RVO. Methods: A total of 50 patients with RVO and 48 healthy subjects with matched sex, age, and education were enrolled in the study. The ReHo method was applied to investigate synchronous neural activity changes in patients with RVO. Results: Compared with HC, patients with RVO showed increased ReHo values in the bilateral cerebellum_4_5. On the contrary, patients with RVO had decreased ReHo values in the bilateral middle occipital gyrus, right cerebelum_crus1, and right inferior temporal gyrus. Conclusion: Our study demonstrated that patients with RVO were associated with abnormal synchronous neural activities in the cerebellum, middle occipital gyrus, and inferior temporal gyrus. These findings shed new insight into neural mechanisms of vision loss in patients with RVO.

Studies on inhibition of respiratory cytochrome bc1 complex by the fungicide pyrimorph suggest a novel inhibitory mechanism.

The respiratory chain cytochrome bc1 complex (cyt bc1) is a major target of numerous antibiotics and fungicides. All cyt bc1 inhibitors act on either the ubiquinol oxidation (QP) or ubiquinone reduction (QN) site. The primary cause of resistance to bc1 inhibitors is target site mutations, creating a need for novel agents that act on alternative sites within the cyt bc1 to overcome resistance. Pyrimorph, a synthetic fungicide, inhibits the growth of a broad range of plant pathogenic fungi, though little is known concerning its mechanism of action. In this study, using isolated mitochondria from pathogenic fungus Phytophthora capsici, we show that pyrimorph blocks mitochondrial electron transport by affecting the function of cyt bc1. Indeed, pyrimorph inhibits the activities of both purified 11-subunit mitochondrial and 4-subunit bacterial bc1 with IC50 values of 85.0 µM and 69.2 µM, respectively, indicating that it targets the essential subunits of cyt bc1 complexes. Using an array of biochemical and spectral methods, we show that pyrimorph acts on an area near the QP site and falls into the category of a mixed-type, noncompetitive inhibitor with respect to the substrate ubiquinol. In silico molecular docking of pyrimorph to cyt b from mammalian and bacterial sources also suggests that pyrimorph binds in the vicinity of the quinol oxidation site.

Icariin promotes extracellular matrix synthesis and gene expression of chondrocytes in vitro.

To effectively treat articular cartilage defect with tissue engineering there is an urgent need to develop safe and cheap drugs that can substitute or cooperate with growth factors for chondrogenesis promotion. Here, we demonstrate the chondrogenic effect of icariin, the major pharmacological active constituent of Herb Epimedium (HEP). Rabbit chondrocytes were isolated from articular cartilage and cultured in vitro with different concentrations of icariin. Icariin at concentrations under 1 × 10⁻5 M showed low cytotoxicity toward chondrocytes, but icariin at 5 × 10⁻5 M inhibited the proliferation of chondrocytes. Icariin hardly affected the cell morphology with concentrations ranging from 1 × 10⁻7 M to 5 × 10⁻5 M. However, the higher concentration of icariin produced more extracellular matrix (ECM) synthesis and expression of chondrogenesis genes of chondrocytes. Indeed, the promotion of icariin on the synthesis of glycosaminoglycans (GAGs) and collagen of chondrocytes, and finally exerting a potent chondrogenic effect, might be due to its ability to up-regulate the expression of aggrecan, collagen II and Sox9 genes and to down-regulate the expression of the collagen I gene of chondrocytes. These preliminary results imply that icariin might be an effective accelerant for chondrogenesis and that icariin-loaded biomaterials might have the potential for cartilage tissue engineering. 1 × 10⁻5 M may be a suitable concentration of icariin with chondrogenic effect for tissue engineering.

[The functional mechanism between the pesticide Pyrimorph and humic acid].

In the present experiment, we mainly discussed the function mechanism between the humic acid and a new kind of fungicide Pyrimorph, aiming to play a positive role in the reduction of contamination caused by pesticides on environment. After the disposition step by step, the humic acid was separated into three parts. Then IR and fluorescence analytical methods were employed to explain the functional mechanism between the pesticide and each part of humic acid. As a result, there are extensive interactions between the three parts of the humic acid and the fungicide Pyrimorph. The interactions between fulvic acid and Pyrimorph are mainly the H-bond and the transfer of the electric charge caused by the C=O of the Pyrimorph and the -OH of the fulvic acid, and the interaction between matomeilon and Pyrimorph is mainly the transfer of the electric charge, and the interaction between humin and Pyrimorph is the weakest. It was showed that the fulvic acid is the most active part in the humic acid. That's to say the intensity of the interaction between the three parts of the humic acid and the fungicide Pyrimorph is smaller and smaller with the order of molecular weight from small to big, namely fulvic acid, matomeilon acid and humin.

[Study on the molecular recognization of fungicide of kresoxim-methyl with beta-cyclodextrin and its derivatives].

The molecular recognition of fungicide of kresoxim-methyl with beta-cyclodextrin (beta-CD), methyl-beta-cyclodextrin (RAMEB)and hydroxypropyl-beta-cyclodextrin (RAMEB) was investigated by using UV-Vis spectroscopy analysis. The effect of temperature and polarity of solvent on the recognition interaction was studied. The driving force and the possible structure of the inclusion complexes were also discussed. The results presented that they formed inclusion complexes with a stoichiometry of 1:1, and the formation constant of inclusion complexes was in the order of Ku(HP-beta-CD)>(beta-CD)Kp(RAMEB) at 298.15 K. Elevation of the temperature triggered a decrease in stability of the inclusion complexes and the value of K(beta-D) was the biggest at > or =303.15 K. The formation constant reduced sharply with the decreasing polarity of the solvent. The standard molar Gibbs energies, enthalpies and entropies were all negative. All the results indicated that the association of the guest molecule with beta-CD was favored by enthalpy changes, and hydrophobicity and hydrogen bond interaction were main driving forces for the inclusion reaction. Our findings provided an important proof for the use of inclusion complexes of kresoxim-methyl with CDs.

Extracellular calmodulin-induced stomatal closure is mediated by heterotrimeric G protein and H2O2.

Extracellular calmodulin (ExtCaM) exerts multiple functions in animals and plants, but the mode of ExtCaM action is not well understood. In this paper, we provide evidence that ExtCaM stimulates a cascade of intracellular signaling events to regulate stomatal movement. Analysis of the changes of cytosolic free Ca2+ ([Ca2+]cyt) and H2O2 in Vicia faba guard cells combined with epidermal strip bioassay suggests that ExtCaM induces an increase in both H2O2 levels and [Ca2+]cyt, leading to a reduction in stomatal aperture. Pharmacological studies implicate heterotrimeric G protein in transmitting the ExtCaM signal, acting upstream of [Ca2+]cyt elevation, and generating H2O2 in guard cell responses. To further test the role of heterotrimeric G protein in ExtCaM signaling in stomatal closure, we checked guard cell responses in the Arabidopsis (Arabidopsis thaliana) Galpha-subunit-null gpa1 mutants and cGalpha overexpression lines. We found that gpa1 mutants were insensitive to ExtCaM stimulation of stomatal closure, whereas cGalpha overexpression enhanced the guard cell response to ExtCaM. Furthermore, gpa1 mutants are impaired in ExtCaM induction of H2O2 generation in guard cells. Taken together, our results strongly suggest that ExtCaM activates an intracellular signaling pathway involving activation of a heterotrimeric G protein, H2O2 generation, and changes in [Ca2+]cyt in the regulation of stomatal movements.