Rna viruses in Blechomonas (Trypanosomatidae) and evolution of Leishmaniavirus
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01.09.2018 |
Grybchuk D.
Kostygov A.
Macedo D.
Votýpka J.
Lukeš J.
Yurchenko V.
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mBio |
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1 |
Ссылка
© 2018 Grybchuk et al. In this work, we analyzed viral prevalence in trypanosomatid parasites (Blechomonas spp.) infecting Siphonaptera and discovered nine species of viruses from three different groups (leishbunyaviruses, narnaviruses, and leishmaniaviruses). Most of the flagellate isolates bore two or three viral types (mixed infections). Although no new viral groups were documented in Blechomonas spp., our findings are important for the comprehension of viral evolution. The discovery of bunyaviruses in blechomonads was anticipated, since these viruses have envelopes facilitating their interspecific transmission and have already been found in various trypanosomatids and metatranscriptomes with trypanosomatid signatures. In this work, we also provided evidence that even representatives of the family Narnaviridae are capable of host switching and evidently have accomplished switches multiple times in the course of their evolution. The most unexpected finding was the presence of leishmaniaviruses, a group previously solely confined to the human pathogens Leishmania spp. From phylogenetic inferences and analyses of the life cycles of Leishmania and Blechomonas, we concluded that a common ancestor of leishmaniaviruses most likely infected Leishmania first and was acquired by Blechomonas by horizontal transfer. Our findings demonstrate that evolution of leishmaniaviruses is more complex than previously thought and includes occasional host switching. IMPORTANCE Flagellates belonging to the genus Leishmania are important human parasites. Some strains of different Leishmania species harbor viruses (leishmaniavi-ruses), which facilitate metastatic spread of the parasites, thus aggravating the disease. Up until now, these viruses were known to be hosted only by Leishmania. Here, we analyzed viral distribution in Blechomonas, a related group of flagellates parasitizing fleas, and revealed that they also bear leishmaniaviruses. Our findings shed light on the entangled evolution of these viruses. In addition, we documented that Blechomonas can be also infected by leishbunyaviruses and narnaviruses, viral groups known from other insects’ flagellates.
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Rabbit plasma metabolomic analysis of Nitroproston®: a multi target natural prostaglandin based-drug
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01.09.2018 |
Shestakova K.
Brito A.
Mesonzhnik N.
Moskaleva N.
Kurynina K.
Grestskaya N.
Serkov I.
Lyubimov I.
Bezuglov V.
Appolonova S.
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Metabolomics |
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0 |
Ссылка
© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Introduction: Nitroproston® is a novel multi-target drug bearing natural prostaglandin E 2 (PGE 2 ) and nitric oxide (NO)-donating fragments for treatment of inflammatory and obstructive diseases (i.e., asthma and obstructive bronchitis). Objectives: To investigate the effects of Nitroproston® administration on plasma metabolomics in vivo. Methods: Experimental in vivo study randomly assigning the target drug (treatment group) or a saline solution without the drug (vehicle control group) to 12 rabbits (n = 6 in each group). Untargeted (5880 initial features; 1869 negative–4011 positive ion peaks; UPLC–IT–TOF/MS) and 84 targeted moieties (Nitroproston® related metabolites, prostaglandins, steroids, purines, pyrimidines and amino acids; HPLC–QQQ–MS/MS) were measured from plasma at 0, 2, 4, 6, 8, 12, 18, 24, 32 and 60 min after administration. Results: PGE 2 , 13,14-dihydro-15-keto-PGE 2 , PGB 2 , 1,3-GDN and 15-keto-PGE 2 increased in the treatment group. Steroids (i.e., cortisone, progesterone), organic acids, 3-oxododecanoic acid, nicotinate d-ribonucleoside, thymidine, the amino acids serine and aspartate, and derivatives pyridinoline, aminoadipic acid and uric acid increased (p < 0.05 AUCROC curve > 0.75) after treatment. Purines (i.e., xanthine, guanine, guanosine), bile acids, acylcarnitines and the amino acids l-tryptophan and l-phenylalanine were decreased. Nitroproston® impacted steroidogenesis, purine metabolism and ammonia recycling pathways, among others. Conclusion: Nitroproston®, a multi action novel drug based on natural prostaglandins, altered metabolites (i.e., guanine, adenine, cortisol, cortisone and aspartate) involved in purine metabolism, urea and ammonia biological cycles, steroidogenesis, among other pathways. Suggested mechanisms of action, metabolic pathway interconnections and useful information to further understand the metabolic effects of prostaglandin administration are presented.
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Nanoparticle-enabled experimentally trained wavelet-domain denoising method for optical coherence tomography
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01.09.2018 |
Dolganova I.
Chernomyrdin N.
Aleksandrova P.
Beshplav S.
Potapov A.
Reshetov I.
Kurlov V.
Tuchin V.
Zaytsev K.
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Journal of Biomedical Optics |
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7 |
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© 2018 Society of Photo-Optical Instrumentation Engineers (SPIE). We present the nanoparticle-enabled experimentally trained wavelet-domain denoising method for optical coherence tomography (OCT). It employs an experimental training algorithm based on imaging of a test-object, made of the colloidal suspension of the monodisperse nanoparticles and contains the microscale inclusions. The geometry and the scattering properties of the test-object are known a priori allowing us to set the criteria for the training algorithm. Using a wide set of the wavelet kernels and the wavelet-domain filtration approaches, the appropriate filter is constructed based on the test-object imaging. We apply the proposed approach and chose an efficient wavelet denoising procedure by considering the combinations of the decomposition basis from five wavelet families with eight types of the filtration threshold. We demonstrate applicability of the wavelet-filtering for the in vitro OCT image of human brain meningioma. The observed results prove high efficiency of the proposed OCT image denoising technique.
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Compartmental modeling of skin transport
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01.09.2018 |
Amarah A.
Petlin D.
Grice J.
Hadgraft J.
Roberts M.
Anissimov Y.
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European Journal of Pharmaceutics and Biopharmaceutics |
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1 |
Ссылка
© 2018 Elsevier B.V. The primary objective of this study is to introduce a simple and flexible mathematical approach which models transport processes in skin using compartments. The main feature of the presented approach is that the rate constants for exchange between compartments are derived from physiologically relevant diffusional transport parameters. This allows for better physical interpretation of the rate constants, and limits the number of parameters for the compartmental model. The resulting compartmental solution is in good agreement with previously published solutions for the diffusion model of skin when ten or more compartments are used. It was found that the new compartmental model with three compartments provided a better fit of the previously publish water penetration data than the diffusion model. Two special cases for which it is difficult to implement the diffusion model were considered using our compartmental approach. In both cases the compartmental model predictions agreed well with the diffusion model.
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Nanoparticle-based delivery of carbamazepine: A promising approach for the treatment of refractory epilepsy
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25.08.2018 |
Zybina A.
Anshakova A.
Malinovskaya J.
Melnikov P.
Baklaushev V.
Chekhonin V.
Maksimenko O.
Titov S.
Balabanyan V.
Kreuter J.
Gelperina S.
Abbasova K.
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International Journal of Pharmaceutics |
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3 |
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© 2018 Elsevier B.V. Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine (CBZ) with the Pgp. This study investigates the effect of the Pgp inhibitor verapamil on the anticonvulsant effect of CBZ and its nanoparticulate formulation in the rat model of isoniazid-induced epilepsy. Verapamil significantly increased the anticonvulsant effect of CBZ and reduced its effective dose by at least 30% (from 30 mg/kg to 20 mg/kg). Binding of carbamazepine to the poloxamer 188-coated PLGA nanoparticles enabled a 30-fold increase of its anticonvulsive effect, as compared to the free drug. The inhibition of Pgp did not influence the effectivity of carbamazepine encapsulated in nanoparticles.
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Enhanced green upconversion luminescence properties of Er<sup>3+</sup>/Yb<sup>3+</sup> co-doped strontium gadolinium silicate oxyapatite phosphor
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15.08.2018 |
Raju G.
Pavitra E.
Bharat L.
Rao G.
Jeon T.
Huh Y.
Han Y.
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Ceramics International |
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1 |
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© 2018 Elsevier Ltd and Techna Group S.r.l. Upconversion Sr2(Gd.98-xEr.02Ybx)8Si6O26 (SGSO:2Er3+/xYb3+) phosphor materials were synthesized using a citrate sol-gel process. X-ray diffraction patterns confirmed their hexagonal structure. Field emission scanning electron microscopy images of SGSO:2Er3+/xYb3+ phosphors depicted submicron particles. The enhanced upconversion luminescence properties of SGSO:2Er3+/xYb3+ phosphors were analysed as a function of Yb3+ ion concentration and laser power. The energy transfer induced enhanced emission of the Er3+/ Yb3+ ions co-doped SGSO phosphors was ascribed to multi-phonon relaxation. The calculated chromaticity coordinates of the SGSO:2Er3+/xYb3+ phosphors showed emissions could be tuned by changing Yb3+ ion concentration. Optimized sample exhibited the chromaticity coordinate values near to the ultra-high definition television standard green emission coordinates.
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Laser microsurgery of cell spheroids: An effective tool for regeneration studying and novel test system in aesthetic medicine
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13.08.2018 |
Kosheleva N.
Ilina I.
Zurina I.
Gorkun A.
Sitnikov D.
Saburina I.
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Proceedings - International Conference Laser Optics 2018, ICLO 2018 |
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0 |
Ссылка
© 2018 IEEE. Technique of laser microsurgery of cell spheroids with nanosecond laser pulses was used to develop a new simple reproducible model for studying regeneration in vitro. Wound restoration accompanying the reparative processes occurred gradually over seven days due to rearrangement of surviving non-proliferating cells. Skin anti-ageing drugs can be tested on the developed model of cell spheroid's regeneration.
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Repair of damaged articular cartilage: Current approaches and future directions
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11.08.2018 |
Medvedeva E.
Grebenik E.
Gornostaeva S.
Telpuhov V.
Lychagin A.
Timashev P.
Chagin A.
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International Journal of Molecular Sciences |
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14 |
Ссылка
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.
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The use of microfluidic technology for cancer applications and liquid biopsy
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10.08.2018 |
Kulasinghe A.
Wu H.
Punyadeera C.
Warkiani M.
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Micromachines |
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3 |
Ссылка
© 2018 by the authors. There is growing awareness for the need of early diagnostic tools to aid in point-of-care testing in cancer. Tumor biopsy remains the conventional means in which to sample a tumor and often presents with challenges and associated risks. Therefore, alternative sources of tumor biomarkers is needed. Liquid biopsy has gained attention due to its non-invasive sampling of tumor tissue and ability to serially assess disease via a simple blood draw over the course of treatment. Among the leading technologies developing liquid biopsy solutions, microfluidics has recently come to the fore. Microfluidic platforms offer cellular separation and analysis platforms that allow for high throughout, high sensitivity and specificity, low sample volumes and reagent costs and precise liquid controlling capabilities. These characteristics make microfluidic technology a promising tool in separating and analyzing circulating tumor biomarkers for diagnosis, prognosis and monitoring. In this review, the characteristics of three kinds of circulating tumor markers will be described in the context of cancer, circulating tumor cells (CTCs), exosomes, and circulating tumor DNA (ctDNA). The review will focus on how the introduction of microfluidic technologies has improved the separation and analysis of these circulating tumor markers.
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QM/MM description of newly selected catalytic bioscavengers against organophosphorus compounds revealed reactivation stimulus mediated by histidine residue in the acyl-binding loop
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03.08.2018 |
Zlobin A.
Mokrushina Y.
Terekhov S.
Zalevsky A.
Bobik T.
Stepanova A.
Aliseychik M.
Kartseva O.
Panteleev S.
Golovin A.
Belogurov A.
Gabibov A.
Smirnov I.
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Frontiers in Pharmacology |
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3 |
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© 2018 Zlobin, Mokrushina, Terekhov, Zalevsky, Bobik, Stepanova, Aliseychik, Kartseva, Panteleev, Golovin, Belogurov, Gabibov and Smirnov. Butyrylcholinesterase (BChE) is considered as an efficient stoichiometric antidote against organophosphorus (OP) poisons. Recently we utilized combination of calculations and ultrahigh-throughput screening (uHTS) to select BChE variants capable of catalytic destruction of OP pesticide paraoxon. The purpose of this study was to elucidate the molecular mechanism underlying enzymatic hydrolysis of paraoxon by BChE variants using hybrid quantum mechanical/molecular mechanical (QM/MM) calculations. Detailed analysis of accomplished QM/MM runs revealed that histidine residues introduced into the acyl-binding loop are always located in close proximity with aspartate residue at position 70. Histidine residue acts as general base thus leading to attacking water molecule activation and subsequent SN2 inline hydrolysis resulting in BChE reactivation. This combination resembles canonical catalytic triad found in active centers of various proteases. Carboxyl group activates histidine residue by altering its pKa, which in turn promotes the activation of water molecule in terms of its nucleophilicity. Observed re-protonation of catalytic serine residue at position 198 from histidine residue at position 438 recovers initial configuration of the enzyme's active center, facilitating next catalytic cycle. We therefore suggest that utilization of uHTS platform in combination with deciphering of molecular mechanisms by QM/MM calculations may significantly improve our knowledge of enzyme function, propose new strategies for enzyme design and open new horizons in generation of catalytic bioscavengers against OP poisons.
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Neuroprotective effects of mitochondria-targeted plastoquinone in a rat model of neonatal hypoxic–ischemic brain injury
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01.08.2018 |
Silachev D.
Plotnikov E.
Pevzner I.
Zorova L.
Balakireva A.
Gulyaev M.
Pirogov Y.
Skulachev V.
Zorov D.
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Molecules |
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6 |
Ссылка
© 2018 by the authors. Neonatal hypoxia–ischemia is one of the main causes of mortality and disability of newborns. To study the mechanisms of neonatal brain cell damage, we used a model of neonatal hypoxia–ischemia in seven-day-old rats, by annealing of the common carotid artery with subsequent hypoxia of 8% oxygen. We demonstrate that neonatal hypoxia–ischemia causes mitochondrial dysfunction associated with high production of reactive oxygen species, which leads to oxidative stress. Targeted delivery of antioxidants to the mitochondria can be an effective therapeutic approach to treat the deleterious effects of brain hypoxia–ischemia. We explored the neuroprotective properties of the mitochondria-targeted antioxidant SkQR1, which is the conjugate of a plant plastoquinone and a penetrating cation, rhodamine 19. Being introduced before or immediately after hypoxia–ischemia, SkQR1 affords neuroprotection as judged by the diminished brain damage and recovery of long-term neurological functions. Using vital sections of the brain, SkQR1 has been shown to reduce the development of oxidative stress. Thus, the mitochondrial-targeted antioxidant derived from plant plastoquinone can effectively protect the brain of newborns both in pre-ischemic and post-stroke conditions, making it a promising candidate for further clinical studies.
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In-vitro antitumor activity of new quaternary phosphonium salts, derivatives of 3-hydroxypyridine
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01.08.2018 |
Iksanova A.
Gabbasova R.
Kupriyanova T.
Akhunzyanov A.
Pugachev M.
Vafiva R.
Shtyrlin N.
Balakin K.
Shtyrlin Y.
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Anti-Cancer Drugs |
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2 |
Ссылка
© 2018 Wolters Kluwer Health, Inc. All rights reserved. This work presents the results of in-vitro biological activity studies of three novel anticancer agents, phosphonium salts based on the 3-hydroxypyridine scaffold, including one derivative of 4-deoxypyridoxine. Proliferation and viability of cells treated with these compounds was assessed by the colony formation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Effects of the compounds on apoptosis and cell cycle were studied by flow cytometry using annexin V-FITC/propidium iodide and propidium iodide staining, respectively. The influence of the compounds on mitochondrial membrane potential and intracellular reactive oxygen species was evaluated using tetramethyl rhodamine ethyl and DCFHA staining. Western blot analysis was used to study the changes in the expression of Bcl-xL, Bax, and caspase-3 apoptotic proteins. The treatment of ovarian adenocarcinoma cells OVCAR-4 with the tested compounds inhibited the growth and induced cell cycle arrest in the G1 phase. 3-Hydroxypyridine derivatives induced apoptosis by hyperexpression of Bax and caspase-3, whereas 4-deoxypyridoxine derivative induced cell death partly by reactive oxygen species generation and caspase-3 hyperexpression. These results indicate that the quaternary phosphonium salts studied represent potential therapeutic agents for the treatment of ovarian cancer.
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A new sample treatment for asialo-Tf determination with capillary electrophoresis: an added value to the analysis of CDT
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01.08.2018 |
Porpiglia N.
De Palo E.
Savchuk S.
Appolonova S.
Bortolotti F.
Tagliaro F.
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Clinica Chimica Acta |
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3 |
Ссылка
© 2018 Background and aim: The non-glycosylated glycoform of transferrin (Tf), known as asialo-Tf, was not selected (in favor of disialo-Tf) as the measurand for the standardization of carbohydrate deficient transferrin (CDT) determination because of a lower diagnostic sensitivity provided with the currently available analytical procedures for sera. However, asialo-Tf could provide an additional value to disialo-Tf in the CDT analysis employed in forensic toxicology contexts. The present work aimed at developing an easy sample preparation based on PEG precipitation in order to improve the detectability of asialo-Tf in capillary electrophoresis (CE). Methods: Equal volumes (35 μL) of serum and of 30% PEG-8000 were mixed and briefly vortexed. After centrifugation, the supernatant was iron saturated with a ferric solution (1:1, v/v). The mixture was analyzed in CE for asialo-Tf and disialo-Tf determination. Results: PEG-8000 precipitation allowed the improvement of the baseline in the electropherograms in terms of interferences reduction particularly in the asialo-Tf migration region. The detection of asialo-Tf was possible in 89% of samples with disialo-Tf above the cut-off limit, whereas only 16% of them showed asialo-Tf by employing the traditional sample preteatment. Conclusions: Asialo-Tf represents an additional value to disialo-Tf as a biomarker of alcohol abuse in forensic toxicology.
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Laparoscopic technique of modified extraperitoneal (Retrotransversalis) end colostomy for abdominoperineal excision
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01.08.2018 |
Tulina I.
Kitsenko Y.
Ubushiev M.
Efetov S.
Wexner S.
Tsarkov P.
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Colorectal Disease |
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0 |
Ссылка
© 2018 The Association of Coloproctology of Great Britain and Ireland. Aim To describe the technique of a modified extraperitoneal retrotransversalis end colostomy as part of a laparoscopic abdominoperineal excision (APR). Method The colostomy site is preoperatively chosen and used intra-operatively for a trocar. After the rectum has been mobilized the descending colon is freed. The peritoneal margin is gently grasped and the parietal peritoneum and extraperitoneal together with the transversalis fascia are separated from the transverse abdominal muscle fibres upwards for 3–4 cm aiming at the trocar site to form the extraperitoneal retrotransversalis canal. The stoma site trocar is partially withdrawn and its head is turned laterally until its tip is positioned in the layer between the abdominal wall muscles and underlying transversalis and extraperitoneal fascia together with the parietal peritoneum. The CO 2 source can be attached so that the gas helps to separate the layers, after which the colostomy trephine is formed at the site of the trocar, the grasper is inserted to gently deliver the blunt end of the descending colon through the canal and the end colostomy is formed in a usual way. Results No procedure-specific complications were noted in 39 patients who had laparoscopic APR with extraperitoneal retrotransversalis end colostomy from 2009 to 2016. In 23 patients who survived for 3.7 ± 1.7 years after surgery there were no clinical or CT signs of parastomal hernia or prolapse. Conclusion This single-institution retrospective case series demonstrates that laparoscopic extraperitoneal retrotransversalis end colostomy is feasible, safe and effective in preventing parastomal hernias and stomal prolapse.
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Structural Alterations in Human Fibroblast Growth Factor Receptors in Carcinogenesis
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01.08.2018 |
Mikhaylenko D.
Alekseev B.
Zaletaev D.
Goncharova R.
Nemtsova M.
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Biochemistry (Moscow) |
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2 |
Ссылка
© 2018, Pleiades Publishing, Ltd. Fibroblast growth factor (FGF) plays an important role in human embryogenesis, angiogenesis, cell proliferation, and differentiation. Carcinogenesis is accompanied by aberrant constitutive activation of FGF receptors (FGFRs) resulting from missense mutation in the FGFR1-4 genes, generation of chimeric oncogenes, FGFR1-4 gene amplification, alternative splicing shift toward formation of mesenchymal FGFR isoforms, and FGFR overexpression. Altogether, these alterations contribute to auto-and paracrine stimulation of cancer cells and neoangiogenesis. Certain missense mutations are found at a high rate in urinary bladder cancer and can be used for non-invasive cancer recurrence diagnostics by analyzing urine cell pellet DNA. Chimeric FGFR1/3 and amplified FGFR1/2 genes can predict cell response to the targeted therapy in various oncological diseases. In recent years, high-throughput sequencing has been used to analyze exomes of virtually all human tumors, which allowed to construct phylogenetic trees of clonal cancer evolution with special emphasis on driver mutations in FGFR1-4 genes. At present, FGFR blockers, such as multi-kinase inhibitors, specific FGFR inhibitors, and FGF ligand traps are being tested in clinical trials. In this review, we discuss current data on the functioning of the FGFR family proteins in both normal and cancer cells, mutations in the FGFR1-4 genes, and mechanisms underlying their oncogenic potential, which might be interesting to a broad range of scientists searching for specific tumor markers and targeted anti-cancer drugs.
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Structure of the complex of cytochrome c with cardiolipin in non-polar environment
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01.08.2018 |
Vladimirov G.
Vikulina A.
Volodkin D.
Vladimirov Y.
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Chemistry and Physics of Lipids |
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3 |
Ссылка
© 2018 Elsevier B.V. The complex of mitochondrial protein cytochrome c (CytC) with anionic phospholipid cardiolipin (CL) plays a crucial role in the initiation of apoptosis by catalyzing lipid peroxidation in mitochondrial membranes. In our previous papers, we found that CytC and CL mixed in millimolar concentrations form a sediment showing microcrystals composed of nanospheres (Cyt-CL) of 11–12 and 8 nm in diameter. The hypothesis was proposed that Cyt-CL, having hydrophobic shell, may appear inside the membrane lipid bilayer in mitochondria and peroxidase membrane phospholipids so initiating the apoptotic cascade. In this work, Cyt-CL complex dissolved in chloroform or hexane was investigated as a model of the complex in mitochondrial membranes. We used dynamic light scattering method to measure the size of the particles. The analysis of particles size distribution of Cyt-CL in chloroform allows to reveal three dominant diameters of 12.1 ± 1.4, 7.8 ± 1.0, and 4.7 ± 0.7 nm. The first two values are closed to those, earlier obtained with small-angle X-ray scattering method in Cyt-CL microcrystals, 11.1 ± 1.0 and 8.0 ± 0.7 nm. CL extracted in chloroform-methanol forms a real solution of particles with diameter of 0.7 ± 0.1 nm. In methanol-water phase, CL and CL + CytC mixture form particles of 83.7 ± 9.8 and 71.3 ± 11.6 nm, respectively. Apparently, cardiolipin in 50% methanol forms single-layer liposomes regardless of the presence of CytC in the medium. Partial unfolding of CytC in the complex was evidenced by (a) appearance of fluorescence of tyrosine and tryptophan residues and (b) disappearance of the absorption band at 699 nm due to breakdown of heme iron – methionine bond > F⋯S(Met80). In hydrophobic solvent Cyt-CL exhibited quasi-lipoperoxidase and lipoxygenase activity as was shown in kinetic measurements of chemiluminescence enhanced by coumarin C-525, a selective sensitizer of chemiluminescence, associated with reactions of lipid peroxyl radicals. Our data in this model system do not contradict the hypothesis (Vladimirov, Y.A. et al. Biochemistry (Mosc) 78, 1086–1097) that nanospheres of Cyt-CL complex, embedded into the lipid phase of mitochondrial membrane, catalyze lipid peroxidation, thereby initiating apoptosis.
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DNA Barcoding of Celyphidae (Diptera) from Vietnam
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01.08.2018 |
Galinskaya T.
Oyun N.
Nartschuk E.
Shatalkin A.
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Russian Journal of Genetics |
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0 |
Ссылка
© 2018, Pleiades Publishing, Inc. The COI gene fragment was first examined in representatives of the family Celyphidae. The presence of a considerable hiatus between interspecific and intraspecific distances was demonstrated, which enabled using the barcoding method to distinguish species of the family Celyphidae. The results of the analysis showed that different species of Celyphidae clustered together. Within the Celyphus (Hemiglobus) porosus cluster, some haplotype heterogeneity, which was, however, within the limits of intraspecific variability, was observed.
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Functionalized folic acid-conjugated amphiphilic alternating copolymer actively targets 3D multicellular tumour spheroids and delivers the hydrophobic drug to the inner core
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01.08.2018 |
Li X.
Sambi M.
Decarlo A.
Burov S.
Akasov R.
Markvicheva E.
Malardier-Jugroot C.
Szewczuk M.
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Nanomaterials |
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3 |
Ссылка
©2018 by the authors. Licensee MDPI, Basel, Switzerland. Engineering of a “smart” drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a “smart” drug delivery system to be specific for a tumour in vivo and to penetrate the inner core remains a major design challenge. These challenges can be overcome by using a study model that integrates the three-dimensional aspect of a tumour in a culture system. Here, we tested the efficacy of a functionalized folic acid-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) to specifically target and penetrate the inner core of three-dimensional avascular human pancreatic and breast tumour spheroids in culture. The copolymer was quantitatively analyzed for its hydrophobic drug encapsulation efficiency using three different chemical drug structures with different molecular weights. Their release profiles and tumour targeting properties at various concentrations and pH environments were also characterized. Using the anticancer drug curcumin and two standard clinical chemotherapeutic hydrophobic drugs, paclitaxel and 5-fluorouracil, we tested the ability of FA-DABA-SMA nanoparticles to encapsulate the differently sized drugs and deliver them to kill monolayer pancreatic cancer cells using the WST-1 cell proliferation assay. The findings of this study revealed that the functionalized folic acid-conjugated amphiphilic alternating copolymer shows unique properties as an active “smart” tumor-targeting drug delivery system with the ability to internalize hydrophobic drugs and release the chemotherapeutics for effective killing of cancer cells. The novelty of the study is the first to demonstrate a functionalized “smart” drug delivery system encapsulated with a hydrophobic drug effectively targeting and penetrating the inner core of pancreatic and breast cancer spheroids and reducing their volumes in a dose-and time-dependent manner.
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Mechanisms of laser activation of chondrocytes in osteoarthritis healing
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01.08.2018 |
Alexandrovskaya Y.
Baum O.
Shekhter A.
Petersen E.
Tiflova O.
Dmitriev A.
Ulyanov V.
Svistushkin V.
Selezneva L.
Sobol E.
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Laser Physics Letters |
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4 |
Ссылка
© 2018 Astro Ltd. Lasers offer new possibilities in the treatment of such widespread diseases as osteoarthritis, with both direct and indirect effects on cell metabolism. Cyclic hydrostatic pressure is one of the main natural stimuli of cartilage chondrocytes. The present work shows that hydrostatic stimulation with magnitudes of up to 20 MPa can be realized locally through infrared impact on the neighboring media of chondrocytes. We compare indirect (thermomechanical, λ = 1560 nm) and direct (photo-modulation, λ1 = 1560 nm, λ2 = 670 nm) laser effects on the synthetic activity of chondrocytes in cultures within a 1 min exposure time limit, to study separately the photo-modulation and thermomechanical components of laser impact. The chondrocyte activity was monitored by immunohistochemical analysis in normoxic and hypoxic conditions. Collagen II and proteoglycan accumulation increased significantly (up to 70%) after a pulsed thermomechanical laser impact. Thermomechanical laser irradiation showed the more pronounced stimulation in both normoxic and hypoxic conditions, while the effect of photo-modulation was inhibited by oxygen concentration increase. Theoretical calculations of the laser-induced temperature and stress fields show that the spreading of the stress field with a maximum at 19.2 MPa is approximately three times greater than that of appreciable (>1 °C) heating. Thus, thermomechanical infrared stimulation of chondrocytes can be a perspective method for the restoration of hyaline-type cartilage.
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The Level of Toxic Elements in Edible Crops from Seleniferous Area (Punjab, India)
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01.08.2018 |
Skalnaya M.
Jaiswal S.
Prakash R.
Prakash N.
Grabeklis A.
Zhegalova I.
Zhang F.
Guo X.
Tinkov A.
Skalny A.
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Biological Trace Element Research |
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© 2017, Springer Science+Business Media, LLC, part of Springer Nature. The primary objective of the present study was to assess the level of selenium and toxic trace elements in wheat, rice, maize, and mustard from seleniferous areas of Punjab, India. The content of selenium (Se) and toxic trace elements, including aluminum (Al), arsenic (As), cadmium (Cd), mercury (Hg), nickel (Ni), lead (Pb), and tin (Sn), in crop samples was assessed using inductively coupled plasma mass-spectrometry after microwave digestion of the samples. The obtained data demonstrate that cultivation of crops on seleniferous soils significantly increased Se level in wheat, mustard, rice, and maize by a factor of more than 590, 111, 85, and 64, respectively. The study also showed that Se exposure affected toxic metal content in crops. In particular, Se-rich wheat was characterized by a significant decrease in Al, As, Ni, Pb, and Sn levels. The level of As, Cd, Ni, Pb, and Sn was significantly decreased in Se-rich rice, whereas As content was increased. In turn, the decrease in Al, As, Cd, Ni, Pb, and Sn levels in Se-rich maize was associated with a significant elevation of Hg content. Finally, Se-rich mustard was characterized by a significant increase in Al, As, and Hg levels, while the content of Ni, Pb, and Sn was significantly lower than the control levels. These findings should be taken into account while developing the nutritional strategies for correction of Se status. At the same time, the exact mechanisms underlying the observed differences are to be estimated.
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