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1. DIABETIC NEUROPATHY: MOLECULAR MECHANISMS OF DEVELOPMENT AND POSSIBILITIES FOR PATHOGENETIC THERAPY

Author

Hudiakova N.V., Ivanov N.V., Pchelin I.Yu., Shishkin A.N., Vorokhobina N.V., Bayrasheva V.K., and Vasilkova V.N.

Subjects
Diabetic neuropathy, pathogenesis, pathogenetic therapy, Science, Medicine, History of scholarship and learning. The humanities, AZ20-999
Abstract

The present review summarizes the results of global studies and assesses contribution of hyperglycemia towards formation of neurologic complications in diabetic patients. Hyperglycemia is believed to play a leading role in the formation of neurological complications in diabetes mellitus. However, the achievement of normalization of glycemia level does not ensure the cessation of their development and progression, which indicates a lack of knowledge about the pathogenetic relationships in diabetic neuropathy. Limited understanding of these issues entails the absence of treatment options that effectively affect the course of this complication. Based on the analysis of experimental and clinical studies of recent years, data on the molecular-biological relationships of hyperglycemia with the formation of neurological complications in diabetes mellitus are summarized. The influence of the oxidative and nitrosative stress, advanced glycation end products, the activation of the polyol and hexosamine pathways on the state of the nerve fiber is analyzed. The data on molecular mechanisms of development of diabetic neuropathy are contradictory. On the basis of recent experimental and clinical data we review possibilities for pathogenetic therapy. The problem of oppositely directed effects of treatment is discussed. Clinical rationale is given for declared direction of further studies.

Published
2019
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3. Comparative analysis of the Squamosa Promoter Binding-Like (SPL) gene family in Nicotiana benthamiana and Nicotiana tabacum

Author

De Paola, C, Garcia-Carpintero, V, Vazquez-Vilar, M, Kaminski, K, Fernandez-del-Carmen, A, Sierro, N, Ivanov, N.V., Giuliano, G., Waterhouse, P., Orzáez Calatayud, Diego, De Paola, C, Garcia-Carpintero, V, Vazquez-Vilar, M, Kaminski, K, Fernandez-del-Carmen, A, Sierro, N, Ivanov, N.V., Giuliano, G., Waterhouse, P., and Orzáez Calatayud, Diego

Abstract

SQUAMOSA PROMOTER BINDING-LIKE (SPL) proteins constitute a large family of transcription factors known to play key roles in growth and developmental processes, including juvenile-to-adult and vegetative-to-reproductive phase transitions. This makes SPLs interesting targets for precision breeding in plants of the Nicotiana genus used as e.g. recombinant biofactories. We report the identification of 49 SPL genes in Nicotiana tabacum cv. K326 and 43 SPL genes in Nicotiana benthamiana LAB strain, which were classified into eight phylogenetic groups according to the SPL classification in Arabidopsis. Exon-intron gene structure and DNA-binding domains were highly conserved between homeologues and orthologues. Thirty of the NbSPL genes and 33 of the NtSPL genes were found to be possible targets of microRNA 156. The expression of SPL genes in leaves was analysed by RNA-seq at three different stages, revealing that genes not under miR156 control were in general constitutively expressed at high levels, whereas miR156-regulated genes showed lower expression, often developmentally regulated. We selected the N. benthamiana SPL13_1a gene as target for a CRISPR/Cas9 knock-out experiment. We show here that a full knock-out in this single gene leads to a significant delay in flowering time, a trait that could be exploited to increase biomass for recombinant protein production.

Published
2023

4. Systems Biology: Methods and Applications

Author

Titz, B., primary, Knorr, A., additional, Sewer, A., additional, Martin, F., additional, Ivanov, N.V., additional, Talikka, M., additional, Gonzalez Suarez, I., additional, Peitsch, M.C., additional, and Hoeng, J., additional

Published
2017
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7. Systems toxicology revealed reduced impact of ths 2.2 aerosol relative to 3R4F smoke on aortic smooth muscle cell aging and exacerbation effects in aged cells in vitro

Author

Poussin, C., primary, Van Der Toorn, M., additional, Scheuner, S., additional, Piault, R., additional, Kondylis, A., additional, Savioz, R., additional, Dulize, R., additional, Peric, D., additional, Guedj, E., additional, Maranzano, F., additional, Merg, C., additional, Morelli, M., additional, Egesipe, A.-L., additional, Johne, S., additional, Majeed, S., additional, Pak, C., additional, Schneider, T., additional, Schlage, W.K., additional, Ivanov, N.V., additional, Peitsch, M.C., additional, and Hoeng, J., additional

Published
2020
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8. Comparison of Pheochromocytoma-Specific Morbidity and Mortality Among Adults With Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy

Author

Neumann, H.P.H., Tsoy, U., Bancos, I., Amodru, V., Walz, M.K., Tirosh, A., Kaur, R.J., McKenzie, T., Qi, X.P., Bandgar, T., Petrov, R., Yukina, M.Y., Roslyakova, A., Horst-Schrivers, A.N.A. van der, Berends, A.M.A., Hoff, A.O., Castroneves, L.A., Ferrara, A.M., Rizzati, S., Mian, C., Dvorakova, S., Hasse-Lazar, K., Kvachenyuk, A., Peczkowska, M., Loli, P., Erenler, F., Krauss, T., Almeida, M.Q., Liu, L.F., Zhu, F.Z., Recasens, M., Wohllk, N., Corssmit, E.P.M., Shafigullina, Z., Calissendorff, J., Grozinsky-Glasberg, S., Kunavisarut, T., Schalin-Jantti, C., Castinetti, F., Vlcek, P., Beltsevich, D., Egorov, V.I., Schiavi, F., Links, T.P., Lechan, R.M., Bausch, B., Young, W.F., Eng, C., Jaiswal, S.K., Zschiedrich, S., Fragoso, M.C.B.V., Pereira, M.A.A., Li, M.H., Costa, J.B., Juhlin, C.C., Gross, D., Violante, A.H.D., Kocjan, T., Ngeow, J., Yoel, U., Fraenkel, M., Simsir, I.Y., Ugurlu, M.U., Ziagaki, A., Diaz, L.R., Kudlai, I.S., Gimm, O., Scherbaum, C.R., Abebe-Campino, G., Barbon, G., Taschin, E., Malinoc, A., Khudiakova, N.V., Ivanov, N.V., Pfeifer, M., Zovato, S., Ploeckinger, U., Makay, O., Grineva, E., Jarzab, B., Januszewicz, A., Shah, N., Seufert, J., Opocher, G., Larsson, C., Int Bilateral-Pheochromocytoma-Reg, Ege Üniversitesi, HUS Abdominal Center, Endokrinologian yksikkö, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Neumann, Hartmut P. H., Tsoy, Uliana, Bancos, Irina, Amodru, Vincent, Walz, Martin K., Tirosh, Amit, Kaur, Ravinder Jeet, McKenzie, Travis, Qi, Xiaoping, Bandgar, Tushar, Petrov, Roman, Yukina, Marina Y., Roslyakova, Anna, van der Horst-Schrivers, Anouk N. A., Berends, Annika M. A., Hoff, Ana O., Castroneves, Luciana Audi, Ferrara, Alfonso Massimiliano, Rizzati, Silvia, Mian, Caterina, Dvorakova, Sarka, Hasse-Lazar, Kornelia, Kvachenyuk, Andrey, Peczkowska, Mariola, Loli, Paola, Erenler, Feyza, Krauss, Tobias, Almeida, Madson Q., Liu, Longfei, Zhu, Feizhou, Recasens, Monica, Wohllk, Nelson, Corssmit, Eleonora P. M., Shafigullina, Zulfiya, Calissendorff, Jan, Grozinsky-Glasberg, Simona, Kunavisarut, Tada, Schalin-Jantti, Camilla, Castinetti, Frederic, Vlcek, Petr, Beltsevich, Dmitry, Egorov, Viacheslav, I, Schiavi, Francesca, Links, Thera P., Lechan, Ronald M., Bausch, Birke, Young, William F., Jr., Eng, Charis, Jaiswal, Sanjeet Kumar, Zschiedrich, Stefan, Fragoso, Maria C. B., V, Pereira, Maria A. A., Li, Minghao, Biarnes Costa, Josefina, Juhlin, Carl Christofer, Gross, David, Violante, Alice H. D., Kocjan, Tomaz, Ngeow, Joanne, Yoel, Uri, Fraenkel, Merav, Simsir, Ilgin Yildirim, Ugurlu, M. Umit, Ziagaki, Athanasia, Robles Diaz, Luis, Kudlai, Inna Stepanovna, Gimm, Oliver, Scherbaum, Christina Rebecca, Abebe-Campino, Gadi, Barbon, Giovanni, Taschin, Elisa, Malinoc, Angelica, Khudiakova, Natalia Valeryevna, Ivanov, Nikita, V, Pfeifer, Marija, Zovato, Stefania, Ploeckinger, Ursula, Makay, Ozer, Grineva, Elena, Jarzab, Barbara, Januszewicz, Andrzej, Shah, Nalini, Seufert, Jochen, Opocher, Giuseppe, Larsson, Catharina, and Lee Kong Chian School of Medicine (LKCMedicine)

Subjects
Male, endocrine system diseases, SURGERY, medicine.medical_treatment, Adrenal Gland Neoplasms, 030230 surgery, Primary Adrenal Insufficiency, 0302 clinical medicine, Interquartile range, Paraganglioma, Registries, Original Investigation, OUTCOMES, integumentary system, Adrenal crisis, Adrenalectomy, General Medicine, GERMLINE MUTATIONS, 3. Good health, Online Only, Diabetes and Endocrinology, PARAGANGLIOMA, CONFER, 030220 oncology & carcinogenesis, Female, medicine.symptom, hormones, hormone substitutes, and hormone antagonists, Adult, medicine.medical_specialty, endocrine system, GENETICS, Urology, Pheochromocytoma, Bilateral Pheochromocytomas, 03 medical and health sciences, Young Adult, medicine, Adrenal insufficiency, MANAGEMENT, Humans, Medicine [Science], RECURRENCE, Retrospective Studies, business.industry, Research, Retrospective cohort study, medicine.disease, PREDISPOSITION, 3121 General medicine, internal medicine and other clinical medicine, Morbidity, Neoplasm Recurrence, Local, business, Organ Sparing Treatments
Abstract

Key Points Question Is cortical-sparing adrenalectomy associated with increased pheochromocytoma-specific morbidity and mortality for patients with bilateral pheochromocytomas compared with total adrenalectomy? Findings In this cohort study of 625 patients with bilateral pheochromocytomas, most had hereditary syndromes, but 36% initially presented with unilateral pheochromocytoma. Bilateral total adrenalectomy resulted in a high rate of adverse effects from glucocorticoid replacement therapy, whereas cortical-sparing surgery was not associated with a worse outcome. Meaning These findings suggest that cortical-sparing surgery may be the preferred approach for patients at risk for, or diagnosed with, bilateral pheochromocytomas, especially those harboring a germline mutation in one of the known predisposition genes., This cohort study compares outcomes associated with cortical-sparing adrenalectomy vs total adrenalectomy for patients with bilateral pheochromocytomas., Importance Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. Objective To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. Design, Setting, and Participants This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. Exposures Total or cortical-sparing adrenalectomy. Main Outcomes and Measures Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. Results Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. Conclusions and Relevance Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma.

Published
2019

9. 3D Vasculature-On-A-Chip: A Model Of Perfused Human Coronary Artery Endothelial Microvessel For Studying Monocyte To Endothelium Adhesion Under Flow

Author

Poussin, C., primary, Kramer, B., additional, Lanz, H., additional, van den Heuvel, A., additional, Laurent, A., additional, Oliver, T., additional, Peric, D., additional, Baumer, K., additional, Dulize, R., additional, Guedj, E., additional, Ivanov, N.V., additional, Peitsch, M.C., additional, Hoeng, J., additional, and Joore, J., additional

Published
2019
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12. Effects of exposure to e-cigarette aerosols compared with cigarette smoke on 3D human buccal and small airway cultures: a systems toxicology assessment

Author

Iskandar, A.R., primary, Sandro, S., additional, Shoaib, M., additional, Kondylis, A., additional, Xiang, Y., additional, Zanetti, F., additional, Frentzel, S., additional, Martin, F., additional, Ivanov, N.V., additional, Peitsch, M.C., additional, Doshi, U., additional, McKinney, W., additional, Lee, M., additional, and Hoeng, J., additional

Published
2018
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13. A clinical research investigation on the effects of cigarette smoking, e- cigarette vaping and smoking cessation on vascular cell biology

Author

Poussin, C., primary, Spinelli, S.L., additional, Curran, T.M., additional, Baglia, L.A., additional, Berg, R., additional, Ansari, S., additional, Guedj, E., additional, Fedlin medlin, L., additional, Ivanov, N.V., additional, Picavet, P., additional, Phipps, R.P., additional, Peitsch, M.C., additional, and Hoeng, J., additional

Published
2018
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16. Toxicological assessment of the mentholated Tobacco Heating System 2.2 – A modified risk tobacco product – In a 90-day inhalation study complemented with systems toxicology

Author

Oviedo, A., primary, Lebrun, S., additional, Ho, J., additional, Tan, W.T., additional, Kogel, U., additional, Leroy, P., additional, Titz, B., additional, Martin, M., additional, Nury, C., additional, Elamin, A., additional, Guedj, E., additional, Ivanov, N.V., additional, Hoeng, J., additional, Peitsch, M.C., additional, and Vanscheeuwijck, P., additional

Published
2016
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17. An application of 3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

Author

Iskandar, A.R., primary, Mathis, C., additional, Martin, F., additional, Leroy, P., additional, Sewer, A., additional, Majeed, S., additional, Kuehn, D., additional, Trivedi, K., additional, Grandolfo, D., additional, Cabanski, M., additional, Guedj, E., additional, Merg, C., additional, Frentzel, S., additional, Ivanov, N.V., additional, Peitsch, M.C., additional, and Hoeng, J., additional

Published
2016
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18. Systems toxicology assessment of a heat-not-burn product aerosol compared with cigarette smoke on organotypic buccal epithelial cultures

Author

Zanetti, F., primary, Schlage, W.K., additional, Sewer, A., additional, Leroy, P., additional, Majeed, S., additional, Guedj, E., additional, Trivedi, K., additional, Elamin, A., additional, Frentzel, S., additional, Iskandar, A.R., additional, Kostadinova, R., additional, Mathis, C., additional, Ivanov, N.V., additional, Peitsch, M.C., additional, and Hoeng, J., additional

Published
2016
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19. Systems toxicological assessment of the mentholated Tobacco Heating System 2.2 aerosol revealed reduced cellular and molecular exposure effects compared with cigarette smoke

Author

Kogel, U., primary, Titz, B., additional, Schlage, W.K., additional, Nury, C., additional, Martin, F., additional, Oviedo, A., additional, Lebrun, S., additional, Elamin, A., additional, Guedj, E., additional, Trivedi, K., additional, Ivanov, N.V., additional, Vanscheeuwijck, P., additional, Peitsch, M.C., additional, and Hoeng, J., additional

Published
2016
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20. Systems toxicology assessment of a heat-not-burn product aerosol compared with conventional cigarette smoke on organotypic bronchial epithelial cultures

Author

Martinez, Y., primary, Mathis, C., additional, Xiang, Y., additional, Leroy, P., additional, Sewer, A., additional, Mejeed, S., additional, Trivedi, K., additional, Guedj, E., additional, Merg, C., additional, Iskandar, A., additional, Schlage, W., additional, Frentzel, S., additional, Ivanov, N.V., additional, Peitsch, M.C., additional, and Hoeng, J., additional

Published
2016
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23. MHD-mode locking by controlled halo-current in the T-10 tokamak

Author

Chudnovskiy, A.N, primary, Gvozdkov, Yu.V, additional, Ivanov, N.V, additional, Kakurin, A.M, additional, Medvedev, A.A, additional, Orlovskiy, I.I, additional, Pavlov, Yu.D, additional, Piterskiy, V.V, additional, Pustovitov, V.D, additional, Safonova, M.B, additional, Volkov, V.V, additional, and Team, T-10, additional

Published
2003
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29. Stabilizing effects of limiter-generated currents in the TO-2 tokamak

Author

Bogdanov, V.F., primary, Gurov, A.A., additional, Ivanov, N.V., additional, Kakurin, A.M., additional, Kovrov, P.E., additional, Martynov, D.A., additional, Mukhin, P.A., additional, Papkov, L.N., additional, Shvindt, N.N., additional, Soloviev, V.E., additional, Volkov, V.V., additional, and Vukolov, K.Yu., additional

Published
1990
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30. Modeling ion interpenetration, stagnation, and thermalization in colliding plasmas.

Author

Jones, Michael E., Winske, D., Goldman, S.R., Kopp, R.A., Rogatchev, V.G., Bel'kov, S.A., Gasparyan, P.D., Dolgoleva, G.V., Zhidkov, N.V., Ivanov, N.V., Kochubej, Yu.K., Nasyrov, G.F., Pavlovskii, V.A., Smirnov, V.V., and Romanov, Yu. A.

Subjects
COLLISIONS (Nuclear physics), PLASMA dynamics
Abstract

Studies ion interpenetration, stagnation and energization processes in colliding laser-produced plasma configurations relevant to Trident experiments. Numerical methods used; Comparison with plasmas generated with gold and deuterated polyethylene targets; Initial expansion of plasmas and their collisional interaction.

Published
1996
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31. Influence of environment on delayed failure of alumina ceramics

Author

Barinov, S.M., Ivanov, N.V., Orlov, S.V., and Shevchenko, V.J.

Abstract

Dynamic fatigue testing of various alumina ceramics in humid air, water, acidic, and alkaline environments was performed. It is shown that the fatigue resistance of glass bonded alumina in air and in water is significantly reduced compared with that for high purity magnesia doped alumina. The crack growth velocity exponent is independent of the composition of the glassy grain boundary phase, as well as of the water content in the environment. Hydrochloric acid slightly lowers the crack growth velocity exponent for yttria–alumosilicate glass bonded ceramics, whereas the exponent decreases drastically for the magnesia doped material in an acidic environment. Possible mechanisms controlling slow crack growth in the ceramics are outlined.

Published
2000
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