State Research Institute Center for Innovative Medicine

Medicine, Lithuania

State Research Institute Center for Innovative Medicine

Medicine, Lithuania
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Jarmalaviciute A.,State Research Institute Center for Innovative Medicine | Pivoriunas A.,State Research Institute Center for Innovative Medicine
Pharmacological Research | Year: 2016

Exosomes are extracellular vesicles that can transfer biological information over long distances affecting normal and pathological processes throughout organism. It is known that very often composition and therapeutic properties of exosomes depends on cell type and its physiological state. Thus, depending on tissue of origin and physiological context exosomes may act as promoters, or suppressors of pathological processes in CNS. From the therapeutic perspective, the most promising cellular sources of exosomes are mesenchymal stem cells, dendritic cells and inducible pluripotent stem cells. In this review, we will summarize the current state of knowledge on the molecular mechanisms underlying neuroprotective actions of exosomes derived from these cells. New therapies for the neurodegenerative disorders are often halted by the inability of drugs to cross blood–brain barrier. In this respect exosomes have a critical advantage, because they can cross blood–brain barrier. Despite the great importance, surprisingly little is known about mechanistic details of this process. Therefore we will discuss some recent findings that may explain mechanisms of exosomal entry into the brain. © 2016 Elsevier Ltd


Valinciute-Jankauskiene A.,State Research Institute Center for Innovative Medicine
Reviews in Medical Microbiology | Year: 2017

: The GB virus C (GBV-C), also referred to as hepatitis G virus, is a RNA hepatitis virus, which infects humans naturally and can cause high levels of viremia, which, however, in most cases, does not lead to serious illness. It is not usually routinely screened in clinical laboratories, though its presence in patients infected with other viruses such as hepatitis C virus and HIV has been commonly reported. The virus can be detected in the blood of infected individuals using reverse-transcription polymerase chain reaction (RT-PCR) mainly. It is a technique that is commonly used for different RNA material detection and other screening such as gene expression and testing. The method includes several steps, that is, transcription of the RNA into complementary DNA (cDNA) by reverse transcriptase, amplification of the cDNA by PCR using well defined primers that target a particular region of the gene, and detection of the PCR products by various means such as agarose gel electrophoresis or hybridization and immunoassay using, for example, automated detection systems. Several primers targeting different regions of the genome, that is, NS3, NS5, and 5’ NTR, have been developed for the amplification of the specific region and the detection of the virus. Moreover, variants of the RT-PCR have been designed to maximize the identification potential. These include, for example, RT-PCR-ELISA, RT digital-PCR, and SYBR green real-time multiplex RT-PCR. Another type of method used to screen the virus is the detection of the presence of antibodies E2 (anti-E2) produced against the viral glycoprotein E2 in individuals who have been infected with the virus and have recovered or are in the process of recovering. The anti-E2s are detected by radio-immunoprecipitation assay and ELISA. Use of both antibody and RNA detection methods is necessary for a better epidemiological investigation of the prevalence of GBV-C. Copyright © Wolters Kluwer Health, Inc. All rights reserved.


Bironaite D.,State Research Institute Center for Innovative Medicine | Brunk U.,Linköping University | Venalis A.,State Research Institute Center for Innovative Medicine
Journal of Cellular Biochemistry | Year: 2013

The involvement of extracellular signal-regulated kinases 1 and 2 (ERK1,2), stress kinase p38 and c-Jun NH2-terminal kinases 1 and 2 (JNK1,2) on Hsp70-upregulation following mild heat shock, and resulting cell protection, was studied on rabbit primary myoblasts. Cells subjected to heat stress (42°C; 60 min) showed a significantly enhanced amount of heat-shock-induced protein 70 (Hsp70), correlating with sustained phosphorylation of MAP kinases ERK1,2, inhibition of p38 and JNK1,2 activation. Induced Hsp70 did not autocrinally suppress activation of transcription factor c-Jun, suggesting involvement of the latter in the protection of myoblasts following heat shock. The inhibition of stress kinases p38, JNK1,2, and MEK1,2 by SP600125, SB203580, and UO126, respectively, established the involvement of JNK1,2 and p38 as upstream, and ERK1,2 as downstream targets of Hsp70 induction. Moreover, the effect of the MEK1,2 inhibitor UO126 revealed a new pathway of c-Jun activation by ERK1,2 in myogenic heat-stressed stem cells. The presented data show that transient activation of JNK1, JNK2, and p38 is necessary for Hsp70 induction and ensuing cell protection. In conclusion, affecting myogenic stem cell protective mechanisms might be a useful strategy in improving stem cell survival and their expanded application in therapy. © 2013 Wiley Periodicals, Inc.


Kvietkauskaite R.,State Research Institute Center for Innovative Medicine | Vaicaitiene R.,Military Medical Service of Lithuanian Armed Forces | Mauricas M.,State Research Institute Center for Innovative Medicine
International Archives of Occupational and Environmental Health | Year: 2014

Purpose: Recent studies have demonstrated various changes in systemic and mucosal immunity in people undergoing psychological stress. This study was designated for an assay of associations between the stress experienced by Lithuanian soldiers as a response to changed job conditions (deployment to Afghanistan) and level of immunoglobulins. Salivary and sera immunoglobulin concentrations were assessed and compared before and after the military mission; the associations between the deployment-related stress and the immunoglobulin level were examined. Methods: Special questionnaires covering state of health and strain experienced were used. Quantitative detection of immunoglobulins was performed by sandwich ELISA. Results: Comparison of the medians at three time points (before, after the deployment and 1 year after the mission) showed an increased level of salivary secretory immunoglobulin A (S-IgA) in association with deployment. Chi-square test of independence indicated statistically significant relationship between the stress and S-IgA amount. Correlation analysis using different health control methods revealed masked fear of soldiers to be expelled from the military service. Conclusions: The results indicated that salivary S-IgA is the most sensitive representative of mucosal immunity system to psychological stress related to changed job conditions in military service. © 2013 Springer-Verlag Berlin Heidelberg.


Bagdonas E.,State Research Institute Center for Innovative Medicine | Raudoniute J.,State Research Institute Center for Innovative Medicine | Bruzauskaite I.,State Research Institute Center for Innovative Medicine | Aldonyte R.,State Research Institute Center for Innovative Medicine
International Journal of COPD | Year: 2015

Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs. Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet. We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade. Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke. The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied. However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between. Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively. Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays. © 2015 Bagdonas et al.


Kausaite-Minkstimiene A.,Vilnius University | Mazeiko V.,Vilnius University | Ramanaviciene A.,Vilnius University | Ramanaviciene A.,State Research Institute Center for Innovative Medicine | And 2 more authors.
Biosensors and Bioelectronics | Year: 2010

In this article a new method for fabrication of enzymatic electrodes suitable for design of amperometric glucose biosensor and/or anode of biofuel cell powered by glucose is presented. Glucose oxidase (GOx) E.C. 1.1.3.4. from Penicillium vitale was immobilized on the carbon rod electrode by cross-linking it with glutaraldehyde (GOx-electrode). Catalytic activity of immobilized GOx was exploited for polymerisation of aniline by taking a high concentration of hydrogen peroxide produced during the catalytic action of immobilized GOx and locally lowered pH due to the formation of gluconic acid; it created optimal conditions for the polymerisation of aniline. The GOx layer was self-encapsulated within formed polyaniline (PANI) matrix (GOx/PANI-electrode). Properties of the GOx/PANI-electrode have been studied and results were compared with GOx-electrode. The results show that the upper detection limit of glucose using GOx-electrode was dramatically changed by the formation of PANI layer. An increase in the upper detection limit, optimal pH region for operation and stability of GOx based electrode modified by PANI was detected when comparing that of an unmodified GOx-electrode. © 2010 Elsevier B.V.


German N.,State Research Institute Center for Innovative Medicine | German N.,Institute of Semiconductor Physics | Ramanavicius A.,Vilnius University | Ramanavicius A.,Institute of Semiconductor Physics | Ramanaviciene A.,Vilnius University
Sensors and Actuators, B: Chemical | Year: 2014

A biosensor based on glucose oxidase (GOx) immobilized on gold nanoparticles (Au-NPs) electrochemically predeposited on the surface of graphite rod (GR) electrode was developed (GOx/Au-NPs/GR). Main analytical characteristics of this biosensor were determined and compared with those determined using a biosensor setup without Au-NP modification (GOx/GR). The highest analytical signal of GOx/Au-NPs/GR electrode was observed after 13 nm Au-NP deposition on the electrode from 0.8 nmol L-1 solution lasting 20 min, when cyclic voltammetry was performed in the range from 0.0 to +1.0 V vs Ag/AgCl. The best analytical characteristics of the developed biosensor were obtained after 25 mg mL-1 GOx immobilization on the Au-NPs/GR electrode. Analytical signal registered using GOx/Au-NPs/GR electrode was 2.08 times higher in comparison to GOx/GR electrode. The registered currents of both electrodes were linearly dependent on glucose concentration in the range of 0.1-10 mmol L-1. The developed GOx/Au-NPs/GR electrode was characterized by high sensitivity, which was equal to 101.02 μA mM -1 cm-2 in the linear glucose detection range. The limit of detection was 0.083 mmol L-1 with relative standard deviation of 6% for GOx/Au-NPs/GR electrode. This study demonstrates a successful practical exploitation of the developed biosensor in a human serum sample. © 2014 Elsevier B.V.


Bratchikov M.,State Research Institute Center for Innovative Medicine | Mauricas M.,State Research Institute Center for Innovative Medicine
Diagnostic Microbiology and Infectious Disease | Year: 2011

A quick and robust Salmonella spp. differentiation method based on high-resolution DNA melting (HRM) was developed. DNA samples from 134 Salmonella spp. strains and 20 serotypes were tested. Each serotype was represented by at least 2 strains. All raw data were derived on the Rotor-Gene 65H0-100 system using the designed 8 primer pairs. The reference samples for HRM error evaluation between runs were applied. Raw data error minimization and fluorescence normalization between runs were carried out by application of the proposed calculations. The data analysis showed that repetitive sequence targets are much more informative than the nonrepetitive ones. The method possesses a high potential and can be adopted for further subtyping analyses. © 2011 Elsevier Inc.


Mieliauskaite D.,State Research Institute Center for Innovative Medicine | Dumalakiene I.,State Research Institute Center for Innovative Medicine | Rugiene R.,State Research Institute Center for Innovative Medicine | MacKiewicz Z.,State Research Institute Center for Innovative Medicine
Clinical and Developmental Immunology | Year: 2012

The main purpose of this study was to determine the expression of interleukins-17/-23 (ILs-17/-23) and receptors of interleukins-17/-23 (IL-17R, IL-23R) in minor salivary glands (MSGs) of patients with primary Sjgren's syndrome (pSS). Expression of IL-17, IL-23 and receptors of IL-17/-23 was analyzed in MSGs from 25 patients with pSS, 25 patients with probable preclinical pSS, and 25 patients with nonautoimmune sicca syndrome by immunohistochemistry. Comparison of the expression of IL-17, IL-23 and receptors of IL-17, IL-23 in MSG of patients with pSS with probable preclinical pSS, and with nonautoimmune sicca syndrome showed significant differences between three groups. However, the expression of IL-17, IL-23 and receptors of IL-17/-23 in MSG was comparable in pSS and probable preclinical pSS patients. We did not find correlation between the expression of IL-17 and IL-23 and of IL-17R and IL-23R in patients with pSS. These results demonstrate an involvement of IL-17/-23 system in the early pSS pathogenesis. Copyright © 2012 Diana Mieliauskaite et al.


Ramanaviciene A.,State Research Institute Center for Innovative Medicine | Ramanaviciene A.,Vilnius University | German N.,State Research Institute Center for Innovative Medicine | Kausaite-Minkstimiene A.,State Research Institute Center for Innovative Medicine | And 4 more authors.
Biosensors and Bioelectronics | Year: 2012

An indirect immunoassay format with human growth hormone (hGH) immobilized on the self-assembled monolayer (SAM) modified surface plasmon resonance (SPR) chip has been shown to detect specific anti-hGH antibodies using the combination of three different physical phenomena in the same channel of the SPR analyzer. For the enhancement of analytical signal and sensitivity of the immunosensor horseradish peroxidase (HRP) labeled secondary antibodies, specifically interacting with the formed immune complexes, were used. The electroassisted chemiluminescence (ECL) protocol offered the limit of detection (LOD) as low as 0.061nM and this result was very similar to that obtained by SPR, which was 0.051nM. In the case of anti-hGH detection using pulsed amperometry (PA) with 3,3',5,5'-tetramethylbenzidine (TMB) and H 2O 2 in the electrochemical system the LOD was the lowest - 0.027nm. Lower reproducibility of the analytical signal and higher limit of detection was observed using cyclic voltammetry (CV) where LOD was 0.056nM. PA detection shows 1.89, 2.07 and 2.26 times higher sensitivity if compared with SPR, CV and ECL, respectively. This work demonstrates successful simultaneous exploitation of several techniques to detect the specific anti-hGH antibodies using indirect immunoassay format on the same area of the SPR-chip. © 2012 Elsevier B.V.

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