TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines

IntroductionT-cell immunoglobulin and mucin domain-3 (TIM-3) is a transmembrane molecule first identified as an immunoregulator. This molecule is also expressed on leukemic cells in acute myeloid leukemia and master cell survival and proliferation. In this study, we aimed to explore the effect of TIM-3 interaction with its ligand galectin-9 (Gal-9) on glucose and lipid metabolism in AML cell lines.MethodsHL-60 and THP-1 cell lines, representing M3 and M5 AML subtypes, respectively, were cultured under appropriate conditions. The expression of TIM-3 on the cell surface was ascertained by flow cytometric assay. We used real-time PCR to examine the mRNA expression of GLUT-1, HK-2, PFKFB-3, G6PD, ACC-1, ATGL, and CPT-1A; colorimetric assays to measure the concentration of glucose, lactate, GSH, and the enzymatic activity of G6PD; MTT assay to determine cellular proliferation; and gas chromatography–mass spectrometry (GC-MS) to designate FFAs.ResultsWe observed the significant upregulated expression of GLUT-1, HK-2, PFKFB-3, ACC-1, CPT-1A, and G6PD and the enzymatic activity of G6PD in a time-dependent manner in the presence of Gal-9 compared to the PMA and control groups in both HL-60 and THP-1 cell lines (p > 0.05). Moreover, the elevation of extracellular free fatty acids, glucose consumption, lactate release, the concentration of cellular glutathione (GSH) and cell proliferation were significantly higher in the presence of Gal-9 compared to the PMA and control groups in both cell lines (p < 0.05).ConclusionTIM-3/Gal-9 ligation on AML cell lines results in aerobic glycolysis and altered lipid metabolism and also protects cells from oxidative stress, all in favor of leukemic cell survival and proliferation

The EROP-Moscow oligopeptide database

Natural oligopeptides may regulate nearly all vital processes. To date, the chemical structures of nearly 6000 oligopeptides have been identified from >1000 organisms representing all the biological kingdoms. We have compiled the known physical, chemical and biological properties of these oligopeptides—whether synthesized on ribosomes or by non-ribosomal enzymes—and have constructed an internet-accessible database, EROP-Moscow (Endogenous Regulatory OligoPeptides), which resides at . This database enables users to perform rapid searches via many key features of the oligopeptides, and to carry out statistical analysis of all the available information. The database lists only those oligopeptides whose chemical structures have been completely determined (directly or by translation from nucleotide sequences). It provides extensive links with the Swiss-Prot-TrEMBL peptide-protein database, as well as with the PubMed biomedical bibliographic database. EROP-Moscow also contains data on many oligopeptides that are absent from other convenient databases, and is designed for extended use in classifying new natural oligopeptides and for production of novel peptide pharmaceuticals

TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines

Introduction: T-cell immunoglobulin and mucin domain-3 (TIM-3) is a transmembrane molecule first identified as an immunoregulator. This molecule is also expressed on leukemic cells in acute myeloid leukemia and master cell survival and proliferation. In this study, we aimed to explore the effect of TIM-3 interaction with its ligand galectin-9 (Gal-9) on glucose and lipid metabolism in AML cell lines. Methods: HL-60 and THP-1 cell lines, representing M3 and M5 AML subtypes, respectively, were cultured under appropriate conditions. The expression of TIM-3 on the cell surface was ascertained by flow cytometric assay. We used real-time PCR to examine the mRNA expression of GLUT-1, HK-2, PFKFB-3, G6PD, ACC-1, ATGL, and CPT-1A; colorimetric assays to measure the concentration of glucose, lactate, GSH, and the enzymatic activity of G6PD; MTT assay to determine cellular proliferation; and gas chromatography–mass spectrometry (GC-MS) to designate FFAs. Results: We observed the significant upregulated expression of GLUT-1, HK-2, PFKFB-3, ACC-1, CPT-1A, and G6PD and the enzymatic activity of G6PD in a time-dependent manner in the presence of Gal-9 compared to the PMA and control groups in both HL-60 and THP-1 cell lines (p > 0.05). Moreover, the elevation of extracellular free fatty acids, glucose consumption, lactate release, the concentration of cellular glutathione (GSH) and cell proliferation were significantly higher in the presence of Gal-9 compared to the PMA and control groups in both cell lines (p < 0.05). Conclusion: TIM-3/Gal-9 ligation on AML cell lines results in aerobic glycolysis and altered lipid metabolism and also protects cells from oxidative stress, all in favor of leukemic cell survival and proliferation.Isfahan University of Medical Science

Солитарный метастаз рака почки в грудном отделе позвоночника: случай из практики

Metastasis of kidney cancer to the bone tissue can be manifested through development of pathological fractures and spinal cord lesions. The clinical case of clear cell renal cell carcinoma with solitary metastasis in the thoracic spine presented in this article demonstrates the possibility of clinical manifestation of the disease through neurological symptoms and the importance of timely comprehensive diagnosis and adherence to treatment deadlines.Метастазирование рака почки в костную ткань может проявляться развитием патологических переломов с поражением спинного мозга. Представленный в настоящей статье клинический случай светлоклеточного почечно-клеточного рака с солитарным метастазированием в грудной отдел позвоночника демонстрирует возможность клинической манифестации болезни с неврологической симптоматики и важность своевременной комплексной диагностики и соблюдения сроков лечения

Mitochondria-targeted antioxidant SkQ1 reverses glaucomatous lesions in rabbits

Original article is published in: Frontiers in Bioscience, Landmark, 20, 892–901, January 1, 2015Glaucoma is the main cause of irreversible blindness worldwide. This disease is characterized by apoptosis of retinal ganglion cells (RGC) and visual field loss that seems to be related to elevated intraocular pressure (IOP). Several lines of evidences have implicated the crucial role of mitochondrial dysfunction in the pathogenesis of glaucoma. Increased mitochondrial oxidative stress in RGC may underlie or contribute to susceptibility of RGC to apoptosis. In our work we (i) designed a rabbit model of chronic, moderately elevated IOP for studying glaucoma and (ii) demonstrated efficacy of mitochondria-targeted antioxidant SkQ1 as a tool to reverse several traits of experimental glaucoma induced by a series of injections of hydroxypropylmethylcellulose (HPMC) to the anterior chamber of the rabbit eye. It is shown that 6 months instillations of drops of 0.2.5–5 µM solution of SkQ1 normalize IOP and eye hydrodynamics and abolish an increase in lens thickness that accompanies glaucoma.Original article is published in: Frontiers in Bioscience, Landmark, 20, 892–901, January 1, 2015Glaucoma is the main cause of irreversible blindness worldwide. This disease is characterized by apoptosis of retinal ganglion cells (RGC) and visual field loss that seems to be related to elevated intraocular pressure (IOP). Several lines of evidences have implicated the crucial role of mitochondrial dysfunction in the pathogenesis of glaucoma. Increased mitochondrial oxidative stress in RGC may underlie or contribute to susceptibility of RGC to apoptosis. In our work we (i) designed a rabbit model of chronic, moderately elevated IOP for studying glaucoma and (ii) demonstrated efficacy of mitochondria-targeted antioxidant SkQ1 as a tool to reverse several traits of experimental glaucoma induced by a series of injections of hydroxypropylmethylcellulose (HPMC) to the anterior chamber of the rabbit eye. It is shown that 6 months instillations of drops of 0.2.5–5 µM solution of SkQ1 normalize IOP and eye hydrodynamics and abolish an increase in lens thickness that accompanies glaucoma

New trends in peptide-based anti-biofilm strategies : a review of recent achievements and bioinformatics approaches

Antimicrobial peptides (AMPs) have a broad spectrum of activity and unspecific mechanisms of action. Therefore, they are seen as valid alternatives to overcome clinically relevant biofilms and reduce the chance of acquired resistance. This paper reviews AMPs and anti-biofilm AMP-based strategies and discusses ongoing and future work. Recent studies report successful AMP-based prophylactic and therapeutic strategies, several databases catalogue AMP information and analysis tools, and novel bioinformatics tools are supporting AMP discovery and design. However, most AMP studies are performed with planktonic cultures, and most studies on sessile cells test AMPs on growing rather than mature biofilms. Promising preliminary synergistic studies have to be consubstantiated and the study of functionalized coatings with AMPs must be further explored. Standardized operating protocols, to enforce the repeatability and reproducibility of AMP anti-biofilm tests, and automated means of screening and processing the ever-expanding literature are still missing.Financial support from IBB-CEB and Fundacao para a Ciencia e Tecnologia (FCT) and European Community fund FEDER, through Program COMPETE, in the ambit of the FCT project 'PTDC/SAU-SAP/113196/2009/ FCOMP-01-0124-FEDER-016012' is gratefully acknowledged

RNA-binding properties and membrane insertion of Melon necrotic spot virus (MNSV) double gene block movement proteins

Advances in structural and biochemical properties of carmovirus movement proteins (MPs) have only been obtained in p7 and p9 from Carnation mottle virus (CarMV). Alignment of carmovirus MPs revealed a low conservation of amino acid identity but interestingly, similarity was elevated in regions associated with the functional secondary structure elements reported for CarMV which were conserved in all studied proteins. Nevertheless, some differential features in relation with CarMV MPs were identified in those from Melon necrotic virus (MNSV) (p7A and p7B). p7A was a soluble non-sequence specific RNA-binding protein, but unlike CarMV p7, its central region alone could not account for the RNA-binding properties of the entire protein. In fact, a 22-amino acid synthetic peptide whose sequence corresponds to this central region rendered an apparent dissociation constant (K(d)) significantly higher than that of the corresponding entire protein (9 mM vs. 0.83-25.7 microM). This p7A-derived peptide could be induced to fold into an alpha-helical structure as demonstrated for other carmovirus p7-like proteins. Additionally, in vitro fractionation of p7B transcription/translation mixtures in the presence of ER-derived microsomal membranes strongly suggested that p7B is an integral membrane protein. Both characteristics of these two small MPs forming the double gene block (DGB) of MNSV are discussed in the context of the intra- and intercellular movement of carmovirus

ХИРУРГИЧЕСКОЕ ЛЕЧЕНИЕ МЕТАСТАЗОВ РАКА ПОЧКИ В ДЛИННЫЕ ТРУБЧАТЫЕ КОСТИ

The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.Проведен ретроспективный анализ данных 35 больных раком почки с метастатическим поражением длинных трубчатых костей, перенесших оперативное лечение. Выполнена оценка роли оперативного лечения у больных с костными метастазами рака почки в длинные трубчатые кости и установлено, что применение данного метода лечения позволяет добиться удовлетворительных результатов в улучшении качества жизни больных, а также увеличения показателей выживаемости у пациентов с солитарными метастазами