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- [Effect of peptide bioregulator and cobalt ions on the activity of NORs and associations of acrocentric chromosomes in lymphocytes of patients with hypertrophic cardiomyopathy and their relatives.] [JOURNAL ARTICLE]
- Georgian Med News 2014 Sep; (234):134-137.
The influence of peptide bioregulator - Livagen (Lys-Glu-Asp-Ala) separately and combined with cobalt ions, on the activity of nucleolar organizer regions (NORs) and frequency of associations of acrocentric chromosomes in lymphocytes from patients with hypertrophic cardiomyopathy (HCM) and their relatives has been studied. It is shown that combined action of Livagen and cobalt ions increases the frequency of large-sized scoring 2 NORs in both, patients and their relatives. Significant was also the influence of the studied compounds on associative activity of acrocsentric chromosomes that was expressed in sharp increase of this indicator in both studied groups. In this case more effective was the action of Livagen and cobalt ions. As activity of NOR, also the frequency of associations of acrocentric chromosomes is dependent of quality of acrocentric chromosome stalk condensation, we conclude, that by influence of Livagen and cobalt ions on the lymphocytes of HCM patients and their relatives, occurs decondensation of heterochromatinized chromatin. This may be release condition during condensation of inactivated genes in the studied groups of individuals. Our data are important because it provides new information about protective effect of Livagen and Livagen+Cobalt ions on the lymphocytes of HCM patients and their relatives and may lead to the development of a therapeutic treatment.
- Clinical relevance of patency capsule combined with abdominal ultrasonography to detect small bowel strictures. [JOURNAL ARTICLE]
- Eur J Gastroenterol Hepatol 2014 Oct 21.
PillCam patency capsule (PC) is a novel and radiofrequency identification tag-free device that remains intact in the gastrointestinal tract for 30-33 h after ingestion and then disintegrates. The aim of this study was to determine the clinical relevance of PC combined with abdominal ultrasonography as a reliable indicator of functional patency.The study was prospective and PillCam PC was administered to consecutive patients with known or suspected small bowel strictures. PC was verified if it was excreted intact in 33 h after administration. Following excretion failure and radiograph detection in the pelvic cavity, ultrasonography was used to detect the PC in relation to the stricture.The participants were 52 patients with known or suspected small bowel strictures (58% women, mean age 51 years, including 32 with or suspected Crohn's disease). Twenty-two patients (42.3%) retrieved PC in the stool within 33 h after ingestion. Radiograph identified the four PCs in the colon and eight were not observed. Ultrasonography precisely judged all 17 PCs retained including six PCs at the proximal side of small bowel stricture in the patients considered ineligible for capsule endoscopy (CE). In all eligible patients, CE passed through the small intestine without incident.PillCam PC combined with ultrasonography before CE appears to be a reliable indicator of functional patency to predict and minimize the risk of impaction in suspected or even known cases with small bowel stricture.
- Effects of Traditional Flood Irrigation on Invertebrates in Lowland Meadows. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110854.
Lowland meadow irrigation used to be widespread in Central Europe, but has largely been abandoned during the 20th century. As a result of agri-environment schemes and nature conservation efforts, meadow irrigation is now being re-established in some European regions. In the absence of natural flood events, irrigation is expected to favour fauna typical of lowland wet meadows. We analysed the effects of traditional flood irrigation on diversity, densities and species composition of three invertebrate indicator taxa in lowland meadows in Germany. Unexpectedly, alpha diversity (species richness and Simpson diversity) and beta diversity (multivariate homogeneity of group dispersions) of orthopterans, carabids, and spiders were not significantly different between irrigated and non-irrigated meadows. However, spider densities were significantly higher in irrigated meadows. Furthermore, irrigation and elevated humidity affected species composition and shifted assemblages towards moisture-dependent species. The number of species of conservation concern, however, did not differ between irrigated and non-irrigated meadows. More variable and intensive (higher duration and/or frequency) flooding regimes might provide stronger conservation benefits, additional species and enhance habitat heterogeneity on a landscape scale.
- Comparative Immune Phenotypic Analysis of Cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in Immune-Competent Individuals: Proportional Representation of CD8+ T-Cells but Not FoxP3+ Regulatory T-Cells Is Associated with Disease Stage. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110928.
Squamous Cell Carcinoma (SCC) is a type of non-melanoma skin cancer prevalent in immune-suppressed transplant recipients and older individuals with a history of chronic sun-exposure. SCC itself is believed to be a late-stage manifestation that can develop from premalignant lesions including Intraepidermal Carcinoma (IEC). Notably, while SCC regression is rare, IEC typically regresses in response to immune modifying topical treatments, however the underlying immunological reasons for these differential responses remain unclear. This study aimed to define whether IEC and SCC are associated with distinct immune profiles. We investigated the immune cell infiltrate of photo-damaged skin, IEC, and SCC tissue using 10-colour flow cytometry following fresh lesion digest. We found that IEC lesions contain higher percentages of CD3+ T-cells than photo-damaged skin, however, the abundance of CD3-CD56+ Natural Killer (NK) cells, CD11c+HLA-DR+ conventional Dendritic Cells (cDC), BDCA-2+HLA-DR+ plasmacytoid DC (pDC), FoxP3+ Regulatory T-cells (T-reg), Vα24+Vβ11+ invariant NKT-cells, and γδ Tcells did not alter with disease stage. Within the total T-cell population, high percentages of CD4+ T-cells were associated with SCC, yet CD8+ T-cells were less abundant in SCC compared with IEC. Our study demonstrates that while IEC lesions contain a higher proportion of T-cells than SCC lesions in general, SCC lesions specifically display a lower abundance of CD8+ T-cells than IEC. We propose that differences in CD8+ T-cell abundance contribute critically to the different capacity of SCC and IEC to regress in response to immune modifying topical treatments. Our study also suggests that a high ratio of CD4+ T-cells to CD8+ T-cells may be a immunological diagnostic indicator of late-stage SCC development in immune-competent patients.
- Myricetin Inhibits the Release of Glutamate in Rat Cerebrocortical Nerve Terminals. [JOURNAL ARTICLE]
- J Med Food 2014 Oct 23.
Abstract The excessive release of glutamate is a critical element in the neuropathology of acute and chronic brain disorders. The purpose of the present study was to investigate the effect and possible mechanism of myricetin, a naturally occurring flavonoid with a neuroprotective profile, on endogenous glutamate release in the nerve terminals (synaptosomes) of the rat cerebral cortex. The release of glutamate was evoked by the K(+) channel blocker 4-aminopyridine (4-AP) and measured by one-line enzyme-coupled fluorometric assay. We also used a membrane potential-sensitive dye to assay the synaptosomal plasma membrane potential, and a Ca(2+) indicator Fura-2 to monitor cytosolic Ca(2+) concentrations ([Ca(2+)]C). Results show that myricetin inhibited 4-AP-evoked glutamate release, and this effect was prevented by chelating extracellular Ca(2+) ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor dl-threo-beta-benzyl-oxyaspartate had no effect on myricetin action. Myricetin did not alter the synaptosomal membrane potential, but decreased 4-AP-induced increases in the cytosolic free Ca(2+) concentration. Furthermore, the myricetin effect on 4-AP-evoked glutamate release was prevented by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking intracellular Ca(2+) release. These results suggest that myricetin inhibits glutamate release from cerebrocortical synaptosomes by attenuating voltage-dependent Ca(2+) entry. This implies that the inhibition of glutamate release is an important pharmacological activity of myricetin that may play a critical role in the apparent clinical efficacy of this compound.
- Target-Responsive DNAzyme Crosslinked Hydrogel for Visual Quantitative Detection of Lead. [JOURNAL ARTICLE]
- Anal Chem 2014 Oct 23.
Because of the severe health risks associated with lead pollution, rapid, sensitive and portable detection of low levels of Pb2+ in biological and environmental samples is of great importance. In this work, a Pb2+ responsive hydrogel was prepared using a DNAzyme and its substrate as crosslinker for rapid, sensitive, portable and quantitative detection of Pb2+. Gold nanoparticles (AuNPs) were first encapsulated in the hydrogel as an indicator for colorimetric analysis. In the absence of lead, the DNAzyme is inactive, and the substrate crosslinker maintains the hydrogel in the gel form. In contrast, the presence of lead activates the DNAzyme to cleave the substrate, decreasing the crosslinking density of the hydrogel and resulting in dissolution of the hydrogel and release of AuNPs for visual detection. As low as 10 nM Pb2+ can be detected by the naked eye. Furthermore, to realize quantitative visual detection, a volumetric bar-chart chip (V-Chip) was used for quantitative readout of the hydrogel system by replacing AuNPs with gold-platinum core-shell nanoparticles (Au@PtNPs). The Au@PtNPs released from the hydrogel upon target activation can efficiently catalyze the decomposition of H2O2 to generate a large volume of O2. The gas pressure moves an ink bar in the V-Chip for portable visual quantitative detection of lead with a detection limit less than 5 nM. The device was able to detect lead in digested blood with excellent accuracy. The method developed can be used for portable lead quantitation in many field applications. Furthermore, the method can be further extended to portable visual quantitative detection of a variety of targets by replacing the lead responsive DNAzyme with other DNAzymes.
- Nephronophthisis-Associated CEP164 Regulates Cell Cycle Progression, Apoptosis and Epithelial-to-Mesenchymal Transition. [JOURNAL ARTICLE]
- PLoS Genet 2014 Oct; 10(10):e1004594.
We recently reported that centrosomal protein 164 (CEP164) regulates both cilia and the DNA damage response in the autosomal recessive polycystic kidney disease nephronophthisis. Here we examine the functional role of CEP164 in nephronophthisis-related ciliopathies and concomitant fibrosis. Live cell imaging of RPE-FUCCI (fluorescent, ubiquitination-based cell cycle indicator) cells after siRNA knockdown of CEP164 revealed an overall quicker cell cycle than control cells, although early S-phase was significantly longer. Follow-up FACS experiments with renal IMCD3 cells confirm that Cep164 siRNA knockdown promotes cells to accumulate in S-phase. We demonstrate that this effect can be rescued by human wild-type CEP164, but not disease-associated mutants. siRNA of CEP164 revealed a proliferation defect over time, as measured by CyQuant assays. The discrepancy between accelerated cell cycle and inhibited overall proliferation could be explained by induction of apoptosis and epithelial-to-mesenchymal transition. Reduction of CEP164 levels induces apoptosis in immunofluorescence, FACS and RT-QPCR experiments. Furthermore, knockdown of Cep164 or overexpression of dominant negative mutant allele CEP164 Q525X induces epithelial-to-mesenchymal transition, and concomitant upregulation of genes associated with fibrosis. Zebrafish injected with cep164 morpholinos likewise manifest developmental abnormalities, impaired DNA damage signaling, apoptosis and a pro-fibrotic response in vivo. This study reveals a novel role for CEP164 in the pathogenesis of nephronophthisis, in which mutations cause ciliary defects coupled with DNA damage induced replicative stress, cell death, and epithelial-to-mesenchymal transition, and suggests that these events drive the characteristic fibrosis observed in nephronophthisis kidneys.
- A Colloidal Singularity Reveals the Crucial Role of Colloidal Stability for Nanomaterials In-Vitro Toxicity Testing: nZVI-Microalgae Colloidal System as a Case Study. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e109645.
Aggregation raises attention in Nanotoxicology due to its methodological implications. Aggregation is a physical symptom of a more general physicochemical condition of colloidal particles, namely, colloidal stability. Colloidal stability is a global indicator of the tendency of a system to reduce its net surface energy, which may be achieved by homo-aggregation or hetero-aggregation, including location at bio-interfaces. However, the role of colloidal stability as a driver of ENM bioactivity has received little consideration thus far. In the present work, which focuses on the toxicity of nanoscaled Fe° nanoparticles (nZVI) towards a model microalga, we demonstrate that colloidal stability is a fundamental driver of ENM bioactivity, comprehensively accounting for otherwise inexplicable differential biological effects. The present work throws light on basic aspects of Nanotoxicology, and reveals a key factor which may reconcile contradictory results on the influence of aggregation in bioactivity of ENMs.
- MS-BWME: A Wireless Real-Time Monitoring System for Brine Well Mining Equipment. [JOURNAL ARTICLE]
- Sensors (Basel) 2014; 14(10):19877-19896.
This paper describes a wireless real-time monitoring system (MS-BWME) to monitor the running state of pumps equipment in brine well mining and prevent potential failures that may produce unexpected interruptions with severe consequences. MS-BWME consists of two units: the ZigBee Wireless Sensors Network (WSN) unit and the real-time remote monitoring unit. MS-BWME was implemented and tested in sampled brine wells mining in Qinghai Province and four kinds of indicators were selected to evaluate the performance of the MS-BWME, i.e., sensor calibration, the system's real-time data reception, Received Signal Strength Indicator (RSSI) and sensor node lifetime. The results show that MS-BWME can accurately judge the running state of the pump equipment by acquiring and transmitting the real-time voltage and electric current data of the equipment from the spot and provide real-time decision support aid to help workers overhaul the equipment in a timely manner and resolve failures that might produce unexpected production down-time. The MS-BWME can also be extended to a wide range of equipment monitoring applications.
- Trends in the Prevalence of Multiple Chronic Conditions in Taiwan From 2000 to 2010: A Population-Based Study. [JOURNAL ARTICLE]
- Prev Chronic Dis 2014.:E187.
Chronic conditions are the leading causes of death and disability worldwide. Providing care to people diagnosed with a chronic disease is challenging, and controlling multiple chronic conditions (MCCs) can be overwhelming, particularly in rapidly aging societies. The objective of this study was to examine the prevalence of MCCs from 2000 to 2010 in Taiwan.A random sample of 1 million representative National Health Insurance beneficiaries in 3 years (2000, 2005, and 2010) was obtained from the Taiwan National Health Insurance Research Database to examine the prevalence of MCCs. Chronic Condition Indicator and Clinical Classifications Software were used to determine and classify codes from the International Classification of Diseases, Ninth Revision. People who had 2 or more conditions among the 15 categories of conditions were defined as having MCCs.The prevalence of MCCs increased from 9.6% in 2000 to 17.1% in 2010. The highest prevalence of MCCs was found among people aged 65 years or older (42.3% in 2000 and 64.5% in 2010, a relative increase of 52.5%). However, the highest rate of increase was found among people younger than 18 years (0.5% in 2000 and 1.6% in 2010, a relative increase of 220.0%).MCCs are increasingly prevalent among the older (≥65 y) population and among children and adolescents. Prevention and early intervention programs targeted to certain age groups may be required. If the increase in MCCs continues rapidly, the management of people diagnosed with MCCs would challenge the capacity of the health care system in Taiwan.