BdERF96 interacts with BdASR1 to specifically respond to drought and oxidative stress in Brachypodium distachyon

Abscisic acid-, stress-, ripening-induced (ASR) proteins are some of the most important small proteins involved in plant responses to abiotic stresses and hormone signals. Recently, BdASR1 was revealed to be upregulated in response to abiotic stresses and hormone treatments and regulate expression of stress-related genes and drought tolerance in tobacco plants. However, the biological and molecular functions of BdASR1 remain to be elucidated. Here, we isolated and characterized BdASR1-interacting protein using the yeast two-hybrid assay. The expression of the interaction protein, BdERF96, increased under drought and oxidative stress corresponding to the expression of BdASR1. Subcellular localization of BdERF96 was detected in the plasma membrane and nucleus. The interaction of BdASR1 and BdERF96 at the plasma membrane and nucleus was demonstrated using bimolecular fluorescence complementation analysis. The findings imply that BdERF96 in association with BdASR1 could play a role in the positive response to drought and oxidative stresses.

     

2-Phenylbenzofuran derivatives alleviate mitochondrial damage via the inhibition of β-amyloid aggregation

To obtain modulators for reducing mitochondrial damage by the inhibition of Aβ oligomer formation, 2-phenylbenzofuran derivatives were designed and prepared. Their inhibitory activity against Aβ fibril formation was screened using ThT fluorescence assay, and the effect of derivatives on mitochondrial function was evaluated using JC-1 and MTT assay. 2-Phenylbenzofuran derivatives with dimethylamino group at p-position had an excellent inhibitory activity against Aβ fibril formation. Particularly, compound 19m alleviated mitochondrial damage remarkably and possessed protective effects against Aβ-induced cytotoxicity.     

Butein,a tetrahydroxychalcone,suppresses pro-inflammatory responses in HaCaT keratinocytes

Up-regulation of cell adhesion molecules and proinflammatory cytokines contributes to enhanced monocyte adhesiveness and infiltration into the skin, during the pathogenesis of various inflammatory skin diseases, including atopic dermatitis. In this study, we examined the anti-inflammatory effects of butein, a tetrahydroxychalcone, and its action mechanisms using TNF-α-stimulated keratinocytes. Butein significantly inhibited TNF-α-induced ICAM-I expression and monocyte adhesion in human keratinocyte cell line HaCaT. Butein also decreased TNF-α-induced pro-inflammatory mediators, such as IL-6, IP-10 and MCP-1, in HaCaT cells. Butein decreased TNF-α-induced ROS generation in a dose-dependent manner in HaCaT cells. In addition, treatment of HaCaT cells with butein suppressed TNF-α-induced MAPK activation. Furthermore, butein suppressed TNF-α-induced NF-kappaB activation. Overall, our results indicate that butein has immunomodulatory activities by inhibiting expression of proinflammatory mediators in keratinocytes. Therefore, butein may be used as a therapeutic agent for the treatment of inflammatory skin diseases. [BMB Reports 2015; 48(9): 495-500]     

Active Immunization with Extracellular Vesicles Derived from Staphylococcus aureus Effectively Protects against Staphylococcal Lung Infections,Mainly via Th1 Cell-Mediated Immunity

Staphylococcus aureus is an important pathogenic bacterium that causes various infectious diseases. Extracellular vesicles (EVs) released from S. aureus contain bacterial proteins, nucleic acids, and lipids. These EVs can induce immune responses leading to similar symptoms as during staphylococcal infection condition and have the potential as vaccination agent. Here, we show that active immunization (vaccination) with S. aureus-derived EVs induce adaptive immunity of antibody and T cell responses. In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells. Moreover, vaccination with S. aureus EVs conferred protection against lethality induced by airway challenge with lethal dose of S. aureus and also pneumonia induced by the administration of sub-lethal dose of S. aureus. These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice. Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17. Together, the study herein suggests that S. aureus EVs are a novel vaccine candidate against S. aureus infections, mainly via Th1 cellular response.     

Advantages of the Phosphatidylserine-Recognizing Peptide PSP1 for Molecular Imaging of Tumor Apoptosis Compared with Annexin V

A number of peptide-based indicators have been identified and reported as potential apoptosis probes, offering great promise for early assessment of therapeutic efficacy in several types of cancer. Direct comparison of the newly developed probes with previously used ones would be an important step in assessing possible applications. Here, we compared the newly identified peptide-based phosphatidylserine (PS) indicator PSP1 (CLSYYPSYC) with annexin V, a common probe for molecular imaging of apoptotic cells, with respect to PS binding kinetics, apoptotic cell-targeting ability, and the efficacy of homing to apoptotic tumor cells in a mouse model after treatment with the anticancer agent camptothecin. Our results indicate that PSP1 efficiently targeted apoptotic cells and generated apoptosis/tumor-specific signals after cancer treatment in the animal model, whereas a similar dose of annexin V showed weak signals. The formation of a stable complex of PSP1 with PS might be one reason for the efficient in vivo targeting. We suggest that PSP1 has potential advantages for in vivo apoptotic cell imaging and could serve as a platform for the development of de novo peptide-based probes for apoptosis.     

Visible Light Induces Melanogenesis in Human Skin through a Photoadaptive Response

Visible light (400–700 nm) lies outside of the spectral range of what photobiologists define as deleterious radiation and as a result few studies have studied the effects of visible light range of wavelengths on skin. This oversight is important considering that during outdoors activities skin is exposed to the full solar spectrum, including visible light, and to multiple exposures at different times and doses. Although the contribution of the UV component of sunlight to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology in terms of inflammation, and limited information is available regarding the role of visible light on pigmentation. The purpose of this study was to determine the effect of visible light on the pro-pigmentation pathways and melanin formation in skin. Exposure to visible light in ex-vivo and clinical studies demonstrated an induction of pigmentation in skin by visible light. Results showed that a single exposure to visible light induced very little pigmentation whereas multiple exposures with visible light resulted in darker and sustained pigmentation. These findings have potential implications on the management of photo-aggravated pigmentary disorders, the proper use of sunscreens, and the treatment of depigmented lesions.     

The Population-Based Risk of Need for Coronary Revascularization According to the Presence of Type 2 Diabetes Mellitus and History of Coronary Heart Disease in the Korean Population

Background

Whether diabetic patients without a history of coronary heart disease (CHD) have the same risk of CHD events as non-diabetic patients with a history of CHD remains controversial. This study aimed to determine whether type 2 diabetes mellitus (T2DM) is a coronary heart disease (CHD) equivalent in the need for coronary revascularization procedures (RVs) in the Korean population.

Methodology/Principal Findings

We followed 2,168,698 subjects who had oral anti-diabetic drugs (OADs)-taking T2DM in 2008 and/or CHD in 2007–2008 (i.e., recent CHD). We used systematic datasets from the nationwide claims database of the Health Insurance Review and Assessment service of Korea, which is representative of the whole population of Korea, from January 2007 to December 2012. The primary study endpoint was the development of need for RVs (i.e., incident CHD) after January 2009 among three groups based on their status of T2DM and recent CHD, i.e., T2DM only, recent CHD only, and both T2DM and recent CHD. After adjustment for age and sex, patients with recent CHD only had 2.14 times the risk of incident CHD (95% CI, 2.11–2.18, P<0.001) compared with patients with T2DM only. Patients with both T2DM and recent CHD demonstrated approximately 2-fold increased risk of incident CHD compared with subjects with recent CHD only (95% CI, 1.75-1.82), while 4-fold increased risk compared with subjects with T2DM only (95% CI, 3.71-3.87). The risk of incident CHD also differed according to sex and age.

Conclusions/Significance

This analysis of data from the nationwide claims database revealed that T2DM did not have a recent CHD equivalent risk in the Korean population. These results suggest that an appropriate strategy for the CHD risk stratification in diabetic patients should be adopted to manage this population.