Reduced cytotoxicity of insulin-immobilized CdS quantum dots using PEG as a spacer

Cytotoxicity is a severe problem for cadmium sulfide nanoparticles (CSNPs) in biological systems. In this study, mercaptoacetic acid-coated CSNPs, typical semiconductor Q-dots, were synthesized in aqueous medium by the arrested precipitation method. Then, amino-terminated polyethylene glycol (PEG) was conjugated to the surface of CSNPs (PCSNPs) in order to introduce amino groups to the surface. Finally, insulin was immobilized on the surface of PCSNPs (ICSNPs) to reduce cytotoxicity as well as to enhance cell compatibility. The presence of insulin on the surface of ICSNPs was confirmed by observing infrared absorptions of amide I and II. The mean diameter of ICSNPs as determined by dynamic light scattering was about 38 nm. Human fibroblasts were cultured in the absence and presence of cadmium sulfide nanoparticles to evaluate cytotoxicity and cell compatibility. The results showed that the cytotoxicity of insulin-immobilized cadmium sulfide nanoparticles was significantly suppressed by usage of PEG as a spacer. In addition, cell proliferation was highly facilitated by the addition of ICSNPs. The ICSNPs used in this study will be potentials to be used in bio-imaging applications

Effect of anthropogenic sulphate aerosol in China on the drought in the western-to-central US

In recent decades, droughts have occurred in the western-to-central United States (US), significantly affecting food production, water supplies, ecosystem health, and the propagation of vector-borne diseases. Previous studies have suggested natural sea surface temperature (SST) forcing in the Pacific as the main driver of precipitation deficits in the US. Here, we show that the aerosol forcing in China, which has been known to alter the regional hydrological cycle in East Asia, may also contribute to reducing the precipitation in the western-to-central US through atmospheric teleconnections across the Pacific. Our model experiments show some indications that both the SST forcing and the increase in regional sulphate forcing in China play a similar role in modulating the western-to-central US precipitation, especially its long-term variation. This result indicates that regional air quality regulations in China have important implications for hydrological cycles in East Asia, as well as in the USopen1

Coherent phonon control via electron-lattice interaction in ferromagnetic Co/Pt multilayers

The manipulation of coherent phonons in condensed systems has attracted fundamental interest, particularly for its applications to future devices. We demonstrate that a coherent phonon in Co/Pt nano-multilayer can be quantitatively controlled via electron-lattice coupling, specifically by changing the multilayer repeat number. To that end, systematic measurement of the time-resolved reflectivity and magneto-optical Kerr effect in Co/Pt multilayers was performed. The coherent phonon frequency was observed to be shifted with the change of the multilayer repeat number. This shift could be clearly explained based on the two-temperature model. Detailed analysis indicated that the lattice heat capacity and electron-lattice coupling strength are linearly dependent on the repeat number of the periodic multilayer structures. Accessing the control of coherent phonons using nanostructures opens a new avenue for advanced phonon-engineering applications.open1131sciescopu

Abdominal wall and labial edema presenting in a girl with Henoch-Schönlein purpura: a case report

<p>Abstract</p> <p>Introduction</p> <p>Henoch-Schönlein purpura is a common immunoglobulin A-mediated vasculitic syndrome in children, characterized by purpuric rash, arthritis and abdominal pain. Renal involvement, manifested by the presence of hematuria and/or proteinuria, is also frequently seen. In most cases, patients with this disease achieve complete recovery, but some progress to renal impairment. Gastro-intestinal manifestations are present in two-thirds of affected patients and range from vomiting, diarrhea, and peri-umbilical pain to serious complications such as intussusception and gastrointestinal hemorrhage.</p> <p>Case presentation</p> <p>We report the case of a 7-year-old Caucasian girl who presented with abdominal pain, labial swelling, and a large abdominal ecchymosis two weeks after having been diagnosed with Henoch-Schönlein purpura. A computed tomography scan revealed abdominal wall edema extending to the groin, without any intra-abdominal pathology. She was successfully treated with intravenous steroids.</p> <p>Conclusion</p> <p>Circumferential anterior abdominal wall edema and labial edema have never been reported previously, to the best of our knowledge, as a complication of Henoch-Schönlein purpura. These findings further contribute to the wide spectrum of manifestations of this disorder in the literature, aiding in its recognition and management.</p

HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. © 2013 Zhang et al

High Cleavage Efficiency of a 2A Peptide Derived from Porcine Teschovirus-1 in Human Cell Lines, Zebrafish and Mice

When expression of more than one gene is required in cells, bicistronic or multicistronic expression vectors have been used. Among various strategies employed to construct bicistronic or multicistronic vectors, an internal ribosomal entry site (IRES) has been widely used. Due to the large size and difference in expression levels between genes before and after IRES, however, a new strategy was required to replace IRES. A self-cleaving 2A peptide could be a good candidate to replace IRES because of its small size and high cleavage efficiency between genes upstream and downstream of the 2A peptide. Despite the advantages of the 2A peptides, its use is not widespread because (i) there are no publicly available cloning vectors harboring a 2A peptide gene and (ii) comprehensive comparison of cleavage efficiency among various 2A peptides reported to date has not been performed in different contexts. Here, we generated four expression plasmids each harboring different 2A peptides derived from the foot-and-mouth disease virus, equine rhinitis A virus, Thosea asigna virus and porcine teschovirus-1, respectively, and evaluated their cleavage efficiency in three commonly used human cell lines, zebrafish embryos and adult mice. Western blotting and confocal microscopic analyses revealed that among the four 2As, the one derived from porcine teschovirus-1 (P2A) has the highest cleavage efficiency in all the contexts examined. We anticipate that the 2A-harboring cloning vectors we generated and the highest efficiency of the P2A peptide we demonstrated would help biomedical researchers easily adopt the 2A technology when bicistronic or multicistronic expression is required

Rosmarinic Acid, Active Component of Dansam-Eum Attenuates Ototoxicity of Cochlear Hair Cells through Blockage of Caspase-1 Activity

Cisplatin causes auditory impairment due to the apoptosis of auditory hair cells. There is no strategy to regulate ototoxicity by cisplatin thus far. Dansam-Eum (DSE) has been used for treating the central nerve system injury including hearing loss in Korea. However, disease-related scientific investigation by DSE has not been elucidated. Here, we demonstrated that DSE and its component rosmarinic acid (RA) were shown to inhibit apoptosis of the primary organ of Corti explants as well as the auditory cells. Administration of DSE and RA reduced the thresholds of the auditory brainstem response in cisplatin-injected mice. A molecular docking simulation and a kinetic assay show that RA controls the activity of caspase-1 by interaction with the active site of caspase-1. Pretreatment of RA inhibited caspase-1 downstream signal pathway, such as the activation of caspase-3 and 9, release of cytochrome c, translocation of apoptosis-inducing factor, up-regulation of Bax, down-regulation of Bcl-2, generation of reactive oxygen species, and activation of nuclear factor-κB. Anticancer activity by cisplatin was not affected by treatment with RA in SNU668, A549, HCT116, and HeLa cells but not B16F10 cells. These findings show that blocking a critical step by RA in apoptosis may be useful strategy to prevent harmful side effects of ototoxicity in patients with having to undergo chemotherapy

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

A quantitative approach to study indirect effects among disease proteins in the human protein interaction network

<p>Abstract</p> <p>Background</p> <p>Systems biology makes it possible to study larger and more intricate systems than before, so it is now possible to look at the molecular basis of several diseases in parallel. Analyzing the interaction network of proteins in the cell can be the key to understand how complex processes lead to diseases. Novel tools in network analysis provide the possibility to quantify the key interacting proteins in large networks as well as proteins that connect them. Here we suggest a new method to study the relationships between topology and functionality of the protein-protein interaction network, by identifying key mediator proteins possibly maintaining indirect relationships among proteins causing various diseases.</p> <p>Results</p> <p>Based on the i2d and OMIM databases, we have constructed (i) a network of proteins causing five selected diseases (DP, disease proteins) plus their interacting partners (IP, non-disease proteins), the DPIP network and (ii) a protein network showing only these IPs and their interactions, the IP network. The five investigated diseases were (1) various cancers, (2) heart diseases, (3) obesity, (4) diabetes and (5) autism. We have quantified the number and strength of IP-mediated indirect effects between the five groups of disease proteins and hypothetically identified the most important mediator proteins linking heart disease to obesity or diabetes in the IP network. The results present the relationship between mediator role and centrality, as well as between mediator role and functional properties of these proteins.</p> <p>Conclusions</p> <p>We show that a protein which plays an important indirect mediator role between two diseases is not necessarily a hub in the PPI network. This may suggest that, even if hub proteins and disease proteins are trivially of great interest, mediators may also deserve more attention, especially if disease-disease associations are to be understood. Identifying the hubs may not be sufficient to understand particular pathways. We have found that the mediators between heart diseases and obesity, as well as heart diseases and diabetes are of relatively high functional importance in the cell. The mediator proteins suggested here should be experimentally tested as products of hypothetical disease-related proteins.</p