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1. Advanced Ultrasound Application – Impact on Presurgical Risk Stratification of the Thyroid Nodules

Author

Stoian D, Ivan V, Sporea I, Florian V, Mozos I, Navolan D, and Nemescu D

Subjects
strain elastography, volumetric doppler, complex ultrasound thyroid evaluation, risk stratification, Therapeutics. Pharmacology, RM1-950
Abstract

Dana Stoian, 1, 2 Viviana Ivan, 1 Ioan Sporea, 1 Varcus Florian, 3 Ioana Mozos, 4 Dan Navolan, 5 Dragos Nemescu 6 1 2nd Department of Internal Medicine, “Victor Babes” University of Medicine, Timisoara, Romania; 2Dr. D Center for Ultrasound in Endocrinology, Timisoara, Romania; 3 2nd Department of Surgery, “Victor Babes” University of Medicine, Timisoara, Romania; 4Department of Physiopathology, “Victor Babes” University of Medicine, Timisoara, Romania; 5Department of Obstetrics Gynecology, “Victor Babes” University of Medicine, Timisoara, Romania; 6Department of Obstetrics Gynecology, “Gr. T. Popa” University of Medicine, Iasi, RomaniaCorrespondence: Dan NavolanDepartment of Obstetrics Gynecology, “Victor Babes” University of Medicine and Pharmacy Timisoara, P-ta Eftimie Murgu, Nr. 2, Timisoara 300011, RomaniaEmail navolan@yahoo.comViviana Ivan 2nd Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, P-ta Eftimie Murgu, Nr. 2, Timisoara 300011, RomaniaTel +40 722 960 911Fax +40 256 020 1890Email ivanmvivi@yahoo.comAim: Current major guidelines recommend risk stratification of the thyroid nodules, after each diagnostic evaluation, in order to focus attention on potentially risky nodules. The main aim of our study was to evaluate the performance of combined advanced ultrasound techniques in this process, compared with conventional stratification models, in order to reduce unnecessary fine-needle biopsies, respectively, surgery.Material and Methods: We evaluated 261 cases (261 nodules) using conventional ultrasound (2B), real-time Doppler evaluation (4D) respectively, real-time elastography, using a linear multifrequency probe and a linear volumetric probe (Hitachi Prerius Machine, Hitachi Inc, Japan). All the nodules were classified using a risk stratification model comprising seven conventional US characteristics, two 4 D characteristics and a color map RTE aspect. The results were compared with the pathology results, considered the golden standard diagnosis.Results: The prevalence of malignant nodules was 21.83% (57 cases). Conventional risk classification generated: 106 low-risk cases, 113 intermediate-risk and 42 high-risk cases. Our proposed risk classification changes the conventional risk classification with a risk upgrade in 27 cases and with a risk downgrade in 69 cases. The diagnostic quality of the combined risk stratification model was better, considering a low-risk category predictive for benignancy and a high category predictive for malignancy: Sensitivity: 80.88% versus 49.01%, respectively, Specificity: 91.22% versus 54.38. The diagnostic power differences were observed regardless of the nodule size.Conclusion: Advanced ultrasound techniques did add diagnostic value in the presurgical risk assessment of the thyroid nodules.Keywords: strain elastography, volumetric Doppler, complex ultrasound thyroid evaluation, risk stratification

Published
2020

2. Two mutations in the thiazide-sensitive NaCl co-transporter gene in a Romanian Gitelman syndrome patient: case report

Author

Gug C, Mihaescu A, and Mozos I

Subjects
Gitelman‘s syndrome, hypokalemia, hypomagnesemia, SLC12A3 gene, consanguinity, Therapeutics. Pharmacology, RM1-950
Abstract

Cristina Gug,1 Adelina Mihaescu,2 Ioana Mozos3,4 1Department of Microscopic Morphology, 22nd Department of Internal Medicine, 3Department of Functional Sciences, 4Center for Translational Research and Systems Medicine, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania Background: Gitelman syndrome (GS) is considered as the most common renal tubular disorder, and we report the first Romanian patient with GS confirmed at molecular level and diagnosed according to genetic testing.Patient and methods: This paper describes the case of a 27-year-old woman admitted with severe hypokalemia, slight hypomagnesemia, hypocalcemia, hypocalciuria, metabolic alkalosis, hyperreninemia, low blood pressure, limb muscle weakness, marked fatigue and palpitations. Family history revealed a consanguineous family with autosomal-recessive transmission of GS with two cases over five generations.Results: Next-generation sequencing technology detected two different homozygous mutations c.1805_1806delAT and c.2660+1G>A in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl co-transporter, confirmed by the Sanger method.Conclusion: Clinicians should be aware of the existence of GS, manage the condition properly and consider the risk of disease recurrence to the next generations. Keywords: Gitelman syndrome, hypokalemia, hypomagnesemia, SLC12A3 gene, consanguinity, hirsutism

Published
2018

3. Therapy with pamidronate in children with osteogenesis imperfecta

Author

Marginean O, Tamasanu RC, Mang N, Mozos I, and Brad GF

Subjects
osteoporosis, child, osteogenesis imperfecta, Pamidronate, Therapeutics. Pharmacology, RM1-950
Abstract

Otilia Marginean,1 Raluca Corina Tamasanu,1 Niculina Mang,1 Ioana Mozos,2,3 Giorgiana Flavia Brad1 1First Department of Pediatrics, 2Department of Functional Sciences, 3Center for Translational Research and Systems Medicine, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania Abstract: Osteogenesis imperfecta (OI) is a genetic disease characterized by excessive bone fragility with fractures consecutive to minor trauma. Considering lack of standardization of therapy with pamidronate in children, it was our aim to present our experience over a period of 10 years regarding evolution and treatment in patients diagnosed with osteoporosis and OI. Nine patients diagnosed with OI were admitted to the First Pediatric Clinic, Timisoara. They were investigated (clinical, biomarkers of bone metabolism and imaging studies), and a quality-of-life questionnaire was used to evaluate the impact of OI. Treatment was performed with pamidronate 1 mg/kg/cycle, every 3 months. The patients were evaluated every 3 months. The most frequent was type III (three patients), and two patients were diagnosed with type II, while the other patients were diagnosed with other forms such as types IV, V, VI and VIII. The clinical expression was polymorphic, and the number of fractures was variable. Bone pain ameliorated just after the first cycle of pamidronate, while the activity and mobility increased quickly. Osteodensitometry in children over 12 years showed a decreased bone mineral density (BMD) with a significant improvement after treatment. The values of the bone alkaline phosphatase and osteocalcin changed after the antiresorptive treatment, and the quality of life of the children and their family improved. Treatment with pamidronate is beneficial for the patient, family and society, increases mobility and bone density, improves quality of life and reduces family dependence in children with OI. Keywords: osteoporosis, child, osteogenesis imperfecta, pamidronate

Published
2017

4. Theme 05 - Human Cell Biology and Pathology.

Author

Balendra, R., Ruiz de los Mozos, I., Odeh, H., Glaria, I., Milioto, C., Wilson, K., Ule, A., Hallegger, M., Masino, L., Martin, S., Patani, R., Shorter, J., Ule, J., Isaacs, A., Liu, F., Vettleson-Trutza, S., Ly, A., Waidmann, J., Oskarsson, B., and Rossoll, W.

Subjects
*HUMAN biology, *CYTOLOGY, *AMYOTROPHIC lateral sclerosis, *PATHOLOGY, *NEURODEGENERATION
Abstract

The article titled "Theme 05 - Human Cell Biology and Pathology" is a comprehensive study conducted by multiple authors on the topic of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The study explores various aspects of these neurodegenerative diseases, including their underlying cellular and molecular mechanisms, genetic factors, and potential therapeutic targets. The research presented in the article provides valuable insights into the pathogenesis of ALS and FTD, which can be beneficial for further research and the development of effective treatments. [Extracted from the article]

Published
2023
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5. U1A is a positive regulator of the expression of heterologous and cellular genes involved in cell proliferation and migration

Author

Rovira E, Moreno B, Razquin N, Hjerpe R, Gonzalez-Lopez M, Barrio R, Ruiz de Los Mozos I, Ule J, Pastor F, Blazquez L, Fortes P.

Subjects
RNA/DNA Editing U1A cell migration proliferation iCLIP U1 snRNP CTGF expression regulation RNA therapy U1i telescripting
Abstract

Here, we show that direct recruitment of U1A to target transcripts can increase gene expression. This is a new regulatory role, in addition to previous knowledge showing that U1A decreases the levels of U1A mRNA and other specific targets. In fact, genome-wide, U1A is more often increasing rather than repressing gene expression and many U1A-upregulated transcripts are directly bound by U1A according to iCLIP studies. Interestingly, U1A-mediated positive regulation can be transferred to a heterologous system for biotechnological purposes. Finally, U1A-bound genes are enriched for those involved in cell cycle and adhesion. In agreement with this, higher U1A mRNA expression associates with lower disease-free survival and overall survival in many cancer types and U1A mRNA levels positively correlate with those of some oncogenes involved in cell proliferation. Accordingly, U1A depletion leads to decreased expression of these genes and the migration related gene CCN2/CTGF, which shows the strongest regulation by U1A. A decrease in U1A causes a strong drop in CCN2 expression and CTGF secretion and defects in the expression of CTGF EMT targets, cell migration and proliferation. These results support U1A as a putative therapeutic target for cancer treatment. In addition, U1A-binding sequences should be considered in biotechnological applications.

Published
2022

6. Arterial stiffness in hematologic malignancies

Author

Mozos I, Borzak G, Caraba A, and Mihaescu R

Subjects
multiple myeloma, arterial stiffness, complete blood count, leukemia, lymphoma, chemotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282
Abstract

Ioana Mozos,1 Georgiana Borzak,2 Alexandru Caraba,3 Rodica Mihaescu3 1Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, 2Department of Hematology, “Oncohelp” Hospital, 3First Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania Abstract: Malignant and cardiovascular disorders are the top causes of mortality worldwide. This article reviews the main literature data and mechanisms linking hematologic malignancies and arterial stiffness, focusing on recent experimental and clinical results. Several links were found in hematologic malignancies between complete blood count and arterial stiffness. Chemotherapy, especially anthracyclines, cyclophosphamide and tyrosine kinase inhibitors, as well as radiotherapy and hematopoietic stem cell transplantation are the main known causes of arterial stiffness increase in hematologic malignancies. The mechanisms of arterial stiffness elevation in hematologic malignancies include an increased oxidative stress, impaired vascular wall homeostasis, endothelial dysfunction and apoptosis of endothelial cells, overexpression of inflammatory cytokines, accelerated atherosclerosis, increased blood viscosity and unstable platelet aggregates. Guidelines regarding cardiovascular health screening and cardiovascular risk scores are necessary for hematologic cancer survivors in order to improve prognosis and quality of life of the patients. Keywords: arterial stiffness, complete blood count, leukemia, lymphoma, multiple myeloma, chemotherapy

Published
2017

10. The regulon of the RNA chaperone CspA and its auto-regulation in Staphylococcus aureus

Author

Caballero, C.J. (Carlos J.), Menendez-Gil, P. (Pilar), Catalan-Moreno, A. (Arancha), Vergara-Irigaray, M. (Marta), García, B. (Begoña), Segura, V. (Víctor), Irurzun, N. (Naiara), Villanueva, M. (Maite), Ruiz-de-los-Mozos, I. (Igor), Solano, C. (Cristina), and Lasa, I. (Íñigo)

Subjects
Fine-tune gene expression, RNA-binding proteins (RBPs)
Abstract

RNA-binding proteins (RBPs) are essential to fine-tune gene expression. RBPs containing the cold-shock domain are RNA chaperones that have been extensively studied. However, the RNA targets and specific functions for many of them remain elusive. Here, combining comparative proteomics and RBP-immunoprecipitation-microarray profiling, we have determined the regulon of the RNA chaperone CspA of Staphylococcus aureus. Functional analysis revealed that proteins involved in carbohydrate and ribonucleotide metabolism, stress response and virulence gene expression were affected by cspA deletion. Stress-associated phenotypes such as increased bacterial aggregation and diminished resistance to oxidative-stress stood out. Integration of the proteome and targetome showed that CspA post-transcriptionally modulates both positively and negatively the expression of its targets, denoting additional functions to the previously proposed translation enhancement. One of these repressed targets was its own mRNA, indicating the presence of a negative post-transcriptional feedback loop. CspA bound the 5'UTR of its own mRNA disrupting a hairpin, which was previously described as an RNase III target. Thus, deletion of the cspA 5'UTR abrogated mRNA processing and auto-regulation. We propose that CspA interacts through a U-rich motif, which is located at the RNase III cleavage site, portraying CspA as a putative RNase III-antagonist.

Published
2018

20. PP.02.23

Author

Mozos, I., primary, Gligor, S., additional, Gotia, L., additional, and Susan, L., additional

Published
2015
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32. Poster Session 2

Author

Andersson, T., primary, Magnusson, A., additional, Bryngelsson, I.- L., additional, Frobert, O., additional, Henriksson, K. M., additional, Edvardsson, N., additional, Poci, D., additional, Polovina, M., additional, Potpara, T., additional, Licina, M., additional, Mujovic, N., additional, Kocijancic, A., additional, Simic, D., additional, Ostojic, M. C., additional, Providencia, R. A., additional, Botelho, A., additional, Trigo, J., additional, Nascimento, J., additional, Quintal, N., additional, Mota, P., additional, Leitao-Marques, A. M., additional, Bosch, R. F., additional, Kirch, W., additional, Rosin, L., additional, Willich, S. N., additional, Pittrow, D., additional, Bonnemeier, H., additional, Valenza, M. C., additional, Martin, L., additional, Munoz Casaubon, T., additional, Valenza, G., additional, Botella, M., additional, Serrano, M., additional, Valenza, B., additional, Cabrera, I., additional, Anderson, K., additional, Benzaquen, B. S., additional, Koziolova, N., additional, Nikonova, J., additional, Shilova, Y., additional, Scherr, D., additional, Narayan, S., additional, Wright, M., additional, Krummen, D., additional, Jadidi, A., additional, Jais, P., additional, Haissaguerre, M., additional, Hocini, M., additional, Hunter, R., additional, Liu, Y., additional, Lu, Y., additional, Wang, W., additional, Schilling, R. J., additional, Bernstein, S., additional, Wong, B., additional, Rooke, R., additional, Vasquez, C., additional, Shah, R., additional, Rosenberg, S., additional, Chinitz, L., additional, Morley, G., additional, Bashir Choudhary, M., additional, Holmqvist, F., additional, Carlson, J., additional, Nilsson, H.- J., additional, Platonov, P. G., additional, Jadidi, A. S., additional, Cochet, H., additional, Miyazaki, S., additional, Shah, A. J., additional, Marrouche, N., additional, Calvo, N., additional, Nadal, M., additional, Andreu, D., additional, Tamborero, D., additional, Diaz, F. E., additional, Berruezo, A., additional, Brugada, J., additional, Mont, L., additional, Fichtner, S., additional, Hessling, G., additional, Estner, H. L., additional, Jilek, C., additional, Reents, T., additional, Ammar, S., additional, Wu, J., additional, Deisenhofer, I., additional, Nakanishi, H., additional, Kashiwase, K., additional, Hirata, A., additional, Wada, M., additional, Ueda, Y., additional, Skoda, J., additional, Neuzil, P., additional, Popelova, J., additional, Petru, J., additional, Sediva, L., additional, Reddy, V. Y., additional, Uldry, L., additional, Forclaz, A., additional, Virag, N., additional, Vesin, J.- M., additional, Kappenberger, L., additional, Sehra, R., additional, Briggs, C., additional, Rappel, W.- J., additional, Janotka, M., additional, Chovanec, M., additional, Yamashiro, K., additional, Takami, K., additional, Sakamoto, Y., additional, Satoh, K., additional, Suzuki, T., additional, Nakagawa, H., additional, Romanov, A., additional, Pokushalov, E., additional, Artemenko, S., additional, Shabanov, V., additional, Stenin, I., additional, Elesin, D., additional, Turov, A., additional, Yakubov, A., additional, Hioki, M., additional, Matsuo, S., additional, Ito, K., additional, Narui, R., additional, Yamashita, S., additional, Sugimoto, K., additional, Yoshimura, M., additional, Yamane, T., additional, Di Biase, L., additional, Gallinghouse, J. D., additional, Rajappan, K., additional, Kautzner, J., additional, Dello Russo, A., additional, Tondo, C., additional, Lorgat, F., additional, Natale, A., additional, Balta, O., additional, Buenz, K., additional, Paessler, M., additional, Anders, H., additional, Horlitz, M., additional, Deneke, T., additional, Lickfett, L., additional, Liberman, I., additional, Linhart, M., additional, Andrie, R., additional, Mittmann-Braun, E., additional, Stockigt, F., additional, Nickenig, G., additional, Schrickel, J., additional, Tilz, R., additional, Rillig, A., additional, Feige, B., additional, Metzner, A., additional, Fuernkranz, A., additional, Burchard, A., additional, Wissner, E., additional, Ouyang, F., additional, Betts, T. R., additional, Jones, M. A., additional, Wong, K. C. K., additional, Qureshi, N., additional, Bashir, Y., additional, Corbucci, G., additional, Losik, D., additional, Selina, V., additional, Crandall, M. A., additional, Daniels, C., additional, Daoud, E., additional, Kalbfleisch, S., additional, Yamaji, H., additional, Murakami, T., additional, Kawamura, H., additional, Murakami, M., additional, Hina, K., additional, Kusachi, S., additional, Dakos, G., additional, Vassilikos, V., additional, Paraskevaidis, S., additional, Mantziari, A., additional, Theophylogiannakos, S., additional, Chouvarda, I., additional, Chatzizisis, I., additional, Styliadis, I., additional, Kimura, T., additional, Fukumoto, K., additional, Nishiyama, N., additional, Aizawa, Y., additional, Fukuda, Y., additional, Sato, T., additional, Miyoshi, S., additional, Takatsuki, S., additional, Navarrete Casas, A. J., additional, Ali, I., additional, Conte, F. C., additional, Moran, M., additional, Graham, B. G., additional, Kalejs, O., additional, Lacis, R., additional, Stradins, P., additional, Koris, A., additional, Putnins, I., additional, Vikmane, M., additional, Lejnieks, A., additional, Erglis, A., additional, Estrada, A., additional, Perez Silva, A., additional, Castrejon, S., additional, Doiny, D., additional, Merino, J. L., additional, Baranchuk, A., additional, Greiss, I., additional, Simpson, C. S., additional, Abdollah, H., additional, Redfearn, D. P., additional, Buys-Topart, M., additional, Nitzsche, R., additional, Thibault, B., additional, Kathan, S., additional, Kolb, C., additional, Reif, S., additional, Schade, S., additional, Taggeselle, J., additional, Frey, A., additional, Birkenhagen, A., additional, Kohler, S., additional, Schmidt, M., additional, Cano Perez, O., additional, Buendia, F., additional, Igual, B., additional, Osca, J. M., additional, Sanchez, J. M., additional, Sancho-Tello, M. J., additional, Olague, J. M., additional, Salvador, A., additional, Tolosana, J. M., additional, Fernandez-Armenta, J., additional, Matas, M., additional, Barbarin, M. C., additional, Habibovic, M., additional, Van Den Broek, K. C., additional, Theuns, D. A. M. J., additional, Jordaens, L., additional, Alings, M., additional, Van Der Voort, P. H., additional, Pedersen, S. S., additional, Pupita, G., additional, Molini, S., additional, Brambatti, M., additional, Capucci, A., additional, Molodykh, S., additional, Idov, E. M., additional, Belyaev, O. V., additional, Segreti, L., additional, Soldati, E., additional, Zucchelli, G., additional, Di Cori, A., additional, Viani, S., additional, Paperini, L., additional, De Lucia, R., additional, Bongiorni, M. G., additional, Binner, L., additional, Taborsky, M., additional, Bello, D., additional, Heuer, H., additional, Ramza, B., additional, Jenniskens, I., additional, Johnson, W. B., additional, Silvetti, M. S., additional, Rava', L., additional, Russo, M. S., additional, Di Mambro, C., additional, Ammirati, A., additional, Gimigliano, G., additional, Prosperi, M., additional, Drago, F., additional, Santos, A. R., additional, Picarra, B., additional, Semedo, P., additional, Dionisio, P., additional, Matos, R., additional, Leitao, M., additional, Jacinto, A., additional, Trinca, M., additional, Mazzone, P., additional, Ciconte, G., additional, Marzi, A., additional, Paglino, G., additional, Vergara, P., additional, Sora, N., additional, Gulletta, S., additional, Della Bella, P., additional, Koppitz, P., additional, Fach, A., additional, Hobbiesiefken, S., additional, Fiehn, E., additional, Hambrecht, R., additional, Sperzel, J., additional, Jung, M., additional, Schmitt, J., additional, Pajitnev, D., additional, Burger, H., additional, Goebel, G., additional, Ehrlich, W., additional, Walther, T., additional, Ziegelhoeffer, T., additional, Vancura, V., additional, Wichterle, D., additional, Melenovsky, V., additional, Glikson, M., additional, Goldenberg, G., additional, Segev, A., additional, Dvir, D., additional, Kuzniec, J., additional, Finkelstein, A., additional, Hay, I., additional, Guetta, V., additional, Choo, W. K., additional, Gupta, S., additional, Kirkfeldt, R., additional, Johansen, J., additional, Nohr, E., additional, Moller, M., additional, Arnsbo, P., additional, Nielsen, J., additional, Banha, M., additional, Stojanov, P., additional, Raspopovic, S., additional, Vasic, D., additional, Savic, D., additional, Nikcevic, G., additional, Jovanovic, V., additional, Defaye, P., additional, Mondesert, B., additional, Mbaye, A., additional, Cassagneau, R., additional, Gagniere, V., additional, Jacon, J., additional, Sanfins, V., additional, Reis, H. R., additional, Nobre, J. N., additional, Martins, V. M., additional, Duarte, L. D., additional, Morais, C. M., additional, Conceicao, J. C., additional, Hero, M., additional, Rey, J. L., additional, Ducharme, A., additional, Simpson, C., additional, Stuglin, C., additional, Blier, L., additional, Senaratne, M., additional, Khaykin, Y., additional, Pinter, A., additional, Mlynarska, A., additional, Mlynarski, R., additional, Sosnowski, M., additional, Wilczek, J., additional, Iorgulescu, C., additional, Bogdan, S., additional, Constantinescu, D., additional, Caldararu, C., additional, Dorobantu, M., additional, Radu, A., additional, Vatasescu, R.- G., additional, Yusu, S., additional, Ikeda, T., additional, Mera, H., additional, Miwa, Y., additional, Abe, A., additional, Miyakoshi, M., additional, Tsukada, T., additional, Yoshino, H., additional, Nayar, V., additional, Cantelon, P., additional, Rawling, A., additional, Belham, M. R. D., additional, Pugh, P. J., additional, Osca Asensi, J., additional, Cano, O., additional, Tejada, D., additional, Munoz, B., additional, Rodriguez, M., additional, Olague, J., additional, Wecke, L., additional, Van Hunnik, A., additional, Thompson, T., additional, Di Carlo, L., additional, Zdeblick, M., additional, Auricchio, A., additional, Prinzen, F., additional, Doltra Magarolas, A., additional, Bijnens, B., additional, Silva, E., additional, Penela, D., additional, Sitges, M., additional, Ofman, P., additional, Navaravong, L., additional, Leng, J., additional, Peralta, A., additional, Hoffmeister, P., additional, Levine, R., additional, Cook, J., additional, Stoenescu, M., additional, Tettamanti, M. E., additional, Revilla Orodea, A., additional, Lopez Diaz, J., additional, De La Fuente Galan, L., additional, Arnold, R., additional, Garcia Moran, E., additional, San Roman Calvar, J. A., additional, Gomez Salvador, I., additional, Nakamura, K., additional, Takami, M., additional, Keida, T., additional, Mesato, A., additional, Higa, S., additional, Shimabukuro, M., additional, Masuzaki, H., additional, Proietti, R., additional, Sagone, A., additional, Domenichini, G., additional, Burri, H., additional, Valzania, C., additional, Biffi, M., additional, Sunthorn, H., additional, Gavaruzzi, G., additional, Foulkes, H., additional, Boriani, G., additional, Koh, S., additional, Hou, W., additional, Snell, J., additional, Poore, J., additional, Dalal, N., additional, Bornzin, G., additional, Kloppe, A., additional, Mijic, D., additional, Bogossian, H., additional, Ninios, I., additional, Zarse, M., additional, Lemke, B., additional, Guedon-Moreau, L., additional, Kouakam, C., additional, Klug, D., additional, Marquie, C., additional, Ziglio, F., additional, Kacet, S., additional, Mohamed Fereig Hamed, H., additional, Hamdy, A. M. A. L., additional, Abd El Aziz, A. H. M. E. D., additional, Nabih, M. R. V. A. T., additional, Hamdy, R. E. H. A. B., additional, Yaminisaharif, A., additional, Davoudi, G. H., additional, Kasemisaeid, A., additional, Sadeghian, S., additional, Vasheghani Farahani, A., additional, Yazdanifard, P., additional, Shafiee, A., additional, Alonso, C., additional, Grimard, C., additional, Jauvert, G., additional, Lazarus, A., additional, Mont, L. L., additional, Ortiz-Perez, J., additional, Caralt, T., additional, Escudero, J., additional, Perez, F., additional, Griffith, K. M., additional, Ferreyra, R., additional, Urena, P., additional, Demas, M., additional, Muratore, C., additional, Mazzetti, H., additional, Guardado, J., additional, Fernandes, M., additional, Pereira, V. H., additional, Canario-Almeida, F., additional, Ferreira, F., additional, Rodrigues, B., additional, Almeida, J., additional, Sokal, A., additional, Jedrzejczyk, E., additional, Lenarczyk, R., additional, Pluta, S., additional, Kowalski, O., additional, Pruszkowska, P., additional, Swiatkowski, A., additional, Kalarus, Z., additional, Heinke, M., additional, Ismer, B., additional, Kuehnert, H., additional, Heinke, T., additional, Surber, R., additional, Osypka, N., additional, Prochnau, D., additional, Figulla, H. R., additional, Iacopino, S., additional, Landolina, M., additional, Proclemer, A., additional, Padeletti, L., additional, Calvi, V., additional, Pierantozzi, A., additional, Di Stefano, P., additional, Bauer, A., additional, Bode, F., additional, Le Gal, F., additional, Deharo, J. C., additional, Delay, M., additional, Clementy, J., additional, Kawamura, M., additional, Munetsugu, Y., additional, Tanno, K., additional, Kobayashi, Y., additional, Cannom, D., additional, Hosoda, J., additional, Ishikawa, T., additional, Andoh, K., additional, Nobuyoshi, M., additional, Fujii, S., additional, Shizuta, S., additional, Isshiki, T., additional, Castel, M. A., additional, Perez-Villa, F., additional, Vidal, B., additional, Pruszkowska-Skrzep, P., additional, Szulik, M., additional, Kukulski, T., additional, Gianfranchi, L., additional, Bettiol, K., additional, Pacchioni, F., additional, Alboni, P., additional, Abu Sham'a, R., additional, Buber, J., additional, Nof, E., additional, Kuperstein, R., additional, Feinberg, M., additional, Luria, D., additional, Eldar, M., additional, Parks, K., additional, Stone, J. R., additional, Singh, J. P., additional, Hatzinikolaou-Kotsakou, E., additional, Kotsakou, M., additional, Beleveslis, T. H., additional, Moschos, G., additional, Reppas, E., additional, Latsios, P., additional, Tsakiridis, K., additional, Kazemisaeid, A., additional, Davoodi, G., additional, Yamini Sharif, A., additional, Sheikhvatan, M., additional, Toniolo, M., additional, Zanotto, G., additional, Rossi, A., additional, Tomasi, L., additional, Vassanelli, C., additional, Versteeg, H., additional, Mommersteeg, P. M. C., additional, Vergara, G., additional, Blauer, J., additional, Ranjan, R., additional, Vijayakumar, S., additional, Kholmovski, E., additional, Volland, N., additional, Macleod, R., additional, Aguinaga Arrascue, L. E., additional, Bravo, A., additional, Garcia Freire, P., additional, Gallardo, P., additional, Hasbani, E., additional, Dantur, J., additional, Quintana, R., additional, Adragao, P. 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G., additional, Schimpf, R., additional, Borggrefe, M., additional, Luesebrink, U., additional, Gardiwal, A., additional, Oswald, H., additional, Koenig, T., additional, Duncker, D., additional, Klein, G., additional, Bastiaenen, R., additional, Batchvarov, V., additional, Atty, O., additional, Cheng, J. H., additional, Behr, E. R., additional, Gallagher, M. M., additional, Starrenburg, A. H., additional, Kraaier, K., additional, Scholten, M. F., additional, Van Der Palen, J., additional, Adhya, S., additional, Smith, L. A., additional, Zhao, T., additional, Bannister, C., additional, Kamdar, R. H., additional, Martinelli, M., additional, Siqueira, S., additional, Greco, R., additional, Nishioka, S. A. D., additional, Pedrosa, A. A. A., additional, Alkmim-Teixeira, R., additional, Peixoto, G. L., additional, Costa, R., additional, Nielsen, J. C., additional, Mortensen, P. T., additional, Johansen, J. B., additional, Kwasniewski, W., additional, Filipecki, A., additional, Urbanczyk-Swic, D., additional, Orszulak, W., additional, Trusz - Gluza, M., additional, Jimenez-Candil, J., additional, Morinigo, J., additional, Ledesma, C., additional, Martin-Luengo, C., additional, Vogtmann, T., additional, Gomer, M., additional, Stiller, S., additional, Kuehlkamp, V., additional, Zach, G., additional, Loescher, S., additional, Kespohl, S., additional, Baumann, G., additional, Snell, J. D., additional, Korsun, N., additional, Snell, J. R., additional, Morley, B., additional, Bharmi, R., additional, Nabutovsky, Y., additional, Mollerus, M., additional, Naslund, L., additional, Meyer, A., additional, Lipinski, M., additional, Libey, B., additional, Dornfeld, K., additional, Martin, A., additional, Gallego, M., additional, De Bie, M. K., additional, Van Rees, J. B., additional, Borleffs, C. J., additional, Thijssen, J., additional, Jukema, J. W., additional, Schalij, M. J., additional, Van Erven, L., additional, Van Der Velde, E. T., additional, Witteman, T. A., additional, Foeken, H., additional, Szili-Torok, T., additional, Akca, F., additional, Caliskan, K., additional, Ten Cate, F., additional, Michels, M., additional, Cozma, D. C., additional, Petrescu, L., additional, Mornos, C., additional, Dragulescu, S. I., additional, Groeneweg, J. A., additional, Velthuis, B. K., additional, Cox, M. G. P. J., additional, Loh, P., additional, Dooijes, D., additional, Cramer, M. J., additional, De Bakker, J. M. T., additional, Hauer, R. N. W., additional, Park, S. D., additional, Shin, S. H., additional, Woo, S. I., additional, Kwan, J., additional, Park, K. S., additional, Kim, D. H., additional, Iorio, A., additional, Vitali Serdoz, L., additional, Brun, F., additional, Daleffe, E., additional, Zecchin, M., additional, Dal Ferro, M., additional, Santangelo, S., additional, Sinagra, G. F., additional, Ouali, S., additional, Hammemi, R., additional, Hammas, S., additional, Kacem, S., additional, Gribaa, R., additional, Neffeti, E., additional, Remedi, F., additional, Boughzela, E., additional, Korantzopoulos, P., additional, Letsas, K., additional, Christogiannis, Z., additional, Kalantzi, K., additional, Ntorkos, A., additional, Goudevenos, J., additional, Foley, P. W. X., additional, Yung, L., additional, Barnes, E., additional, Kikuchi, M., additional, Ito, H., additional, Miyoshi, F., additional, Pecini, R., additional, Marott, J. M., additional, Jensen, G. B., additional, Theilade, J., additional, Mine, T., additional, Kodani, T., additional, Masuyama, T., additional, Mozos, I. M., additional, Serban, C., additional, Costea, C., additional, Susan, L., additional, Barthel, P., additional, Mueller, A., additional, Malik, M., additional, Schmidt, G., additional, Karakurt, O., additional, Kilic, H., additional, Munevver Sari, D. R., additional, Mroczek-Czernecka, D., additional, Pietrucha, A. Z., additional, Borowiec, A., additional, Wnuk, M., additional, Bzukala, I., additional, Kruszelnicka, O., additional, Konduracka, E., additional, Nessler, J., additional, Kikuchi, Y., additional, Meireles, A., additional, Gomes, C., additional, Anjo, D., additional, Roque, C., additional, Pinheiro Vieira, A., additional, Lagarto, V., additional, Hipolito Reis, A., additional, Torres, S., additional, Miller, L., additional, Vedrenne, G., additional, Bruguiere, E., additional, Redheuil, A., additional, Lavergne, T., additional, Le Heuzey, J. Y., additional, Mousseaux, E., additional, Hersi, A., additional, Alhabib, K., additional, Alfaleh, H., additional, Sulaiman, K., additional, Almahmeed, W., additional, Alsuwidi, J., additional, Amin, H., additional, Almotarreb, A., additional, Pang, H. W. K., additional, Michael, K., additional, Pereira, E. J., additional, Munt, P. W., additional, Fitzpatrick, M. F., additional, Revishvili, A. S., additional, Simonyan, G., additional, Dzhordzhikiya, T., additional, Sopov, O., additional, Kalinin, V., additional, Locati, E. T., additional, Vecchi, A. M., additional, Cattafi, G., additional, Sachero, A., additional, Lunati, M., additional, Sayah, S., additional, Alizadeh, A., additional, Nazari, N., additional, Hekmat, M., additional, Moradi, M., additional, Zeighami, M., additional, Ghanji, H., additional, Suzuki, K., additional, Takagi, M., additional, Maeda, K., additional, Tatsumi, H., additional, Vieira, P., additional, Reis, H., additional, Toth, A., additional, Vago, H., additional, Takacs, P., additional, Edes, E., additional, Marki, A., additional, Balazs, G. Y., additional, Huttl, K., additional, Merkely, B., additional, Lainis, F., additional, Buckley, M. M., additional, Johns, E. J., additional, Seifer, C. M., additional, Daba, L., additional, Liebrecht, K., additional, Piwowarska, W., additional, Toquero Ramos, J., additional, Perez Pereira, E., additional, Mitroi, C., additional, Castro Urda, V., additional, Fernandez Villanueva, J. M., additional, Corona Figueroa, A., additional, Hernandez Reina, L., additional, Fernandez Lozano, I., additional, Bartoletti, A., additional, Bocconcelli, P., additional, Giuli, S., additional, Massa, R., additional, Svetlich, C., additional, Tarsi, G., additional, Tronconi, F., additional, Vitale, E., additional, Stryjewski, P., additional, Wegrzynowska, M., additional, Lousinha, A., additional, Labandeiro, J., additional, Antunes, E., additional, Silva, S., additional, Alves, S., additional, Timoteo, A., additional, Oliveira, M., additional, Cruz Ferreira, R., additional, and Jedrzejczyk-Spaho, J., additional

Published
2011
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40. Resveratrol, a popular dietary supplement for human and animal health: Quantitative research literature analysis-a review

Author

Yeung, A. W. K., Aggarwal, B. B., Orhan, I. E., Horbańczuk, O. K., Barreca, D., Battino, M., Belwal, T., Bishayee, A., Daglia, M., Devkota, H. P., Echeverría, J., Balacheva, A., Georgieva, M., Godfrey, K., Gupta, V. K., Horbańczuk, J. O., Huminiecki, L., Jóźwik, A., Strzałkowska, N., Mocan, A., Mozos, I., Nabavi, S. M., Pajpanova, T., Pittalà, V., Feder-Kubis, J., Sampino, S., Silva, A. S., Sheridan, H., Sureda, A., Tewari, D., Wang, D., Weissig, V., Yang, Y., Zengin, G., Shanker, K., Moosavi, M. A., Shah, M. A., Kozuharova, E., Al-Rimawi, F., Durazzo, A., Lucarini, M., Souto, E. B., Santini, A., Malainer, C., Dimitar Djilianov, Tancheva, L. P., Li, H. -B, Gan, R. -Y, Tzvetkov, N. T., Atanasov, A. G., El-Demerdash, A., Universidade do Minho, Yeung, A. W. K., Aggarwal, B. B., Orhan, I. E., Horbanczuk, O. K., Barreca, D., Battino, M., Belwal, T., Bishayee, A., Daglia, M., Devkota, H. P., Echeverria, J., Balacheva, A., Georgieva, M., Godfrey, K., Gupta, V. K., Horbanczuk, J. O., Huminiecki, L., Jozwik, A., Strzalkowska, N., Mocan, A., Mozos, I., Nabavi, S. M., Pajpanova, T., Pittala, V., Feder-Kubis, J., Sampino, S., Silva, A. S., Sheridan, H., Sureda, A., Tewari, D., Wang, D., Weissig, V., Yang, Y., Zengin, G., Shanker, K., Moosavi, M. A., Shah, M. A., Kozuharova, E., Al-Rimawi, F., Durazzo, A., Lucarini, M., Souto, E. B., Santini, A., Malainer, C., Djilianov, D., Tancheva, L. P., Li, H. -B., Gan, R. -Y., Tzvetkov, N. T., Atanasov, A. G., and El-Demerdash, A.

Subjects
Pharmacology, Science & Technology, VOSviewer, Biological activities, Biological activitie, biological activities, food and beverages, resveratrol, Bibliometric, Citation analysis, Citation analysi, Bibliometrics, Resveratrol, citation analysis, Cancer, Web of Science, cancer, bibliometrics, pharmacology
Abstract

Resveratrol is a stilbene-type bioactive molecule with a broad spectrum of reported biological effects. In this sense, the current work provides a comprehensive literature analysis on resveratrol, representing a highly-researched commercially available dietary ingredient. Bibliometric data were identified by means of the search string TOPIC=(resveratrol*) and analyzed with the VOSviewer software, which yielded 17,561 publications extracted from the Web of Science Core Collection electronic database. The ratio of original articles to reviews was 9.5:1. More than half of the overall manuscripts have been published since 2013. Major contributing countries were USA, China, Italy, South Korea, and Spain. Most of the publications appeared in journals specialized in biochemistry and molecular biology, pharmacology and pharmacy, food science technology, cell biology, or oncology. The phytochemicals or phytochemical classes that were frequently mentioned in the keywords of analyzed publications included, in descending order: resveratrol, trans-resveratrol, polyphenols, flavonoids, quercetin, stilbenes, curcumin, piceatannol, cis-resveratrol, and anthocyanins., Atanas G. Atanasov and Dongdong Wang acknowledge the support by the Polish KNOW (Leading National Research Centre) Scientific Consortium “Healthy Animal - Safe Food,” decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015 and the European Union under the European Regional Development Fund (Homing/2017-4/41). Antoni Sureda was supported by the Institute of Health Carlos III (Project CIBEROBN CB12/03/30038)., info:eu-repo/semantics/publishedVersion

44. Flavonoids against the SARS-CoV-2 induced inflammatory storm

Author

Karol Kajo, Robert Prosecky, Ioana Mozos, Raghad Khalid Al-Ishaq, Peter Kubatka, Ali Zarrabi, Kevin Zhai, Mehdi Shakibaei, Milad Ashrafizadeh, Giampiero La Rocca, Peter Kruzliak, Lenka Koklesova, Alena Liskova, Martin Caprnda, Dietrich Büsselberg, Mariam Abotaleb, Vladimir Nosal, Peter Sabaka, David Ullrich, Aranka Brockmueller, Marek Samec, Luis Rodrigo, Samson Mathews Samuel, Liskova A., Samec M., Koklesova L., Samuel S.M., Zhai K., Al-Ishaq R.K., Abotaleb M., Nosal V., Kajo K., Ashrafizadeh M., Zarrabi A., Brockmueller A., Shakibaei M., Sabaka P., Mozos I., Ullrich D., Prosecky R., La Rocca G., Caprnda M., Busselberg D., Rodrigo L., Kruzliak P., and Kubatka P.

Subjects
Settore BIO/17 - Istologia, 0301 basic medicine, Phytochemicals, Anti-Inflammatory Agents, Anti-inflammatory effects, Inflammation, RM1-950, Review, Cytokine storm, Proinflammatory cytokine, Immunomodulation, Endothelial activation, 03 medical and health sciences, 0302 clinical medicine, Immune system, Animals, Humans, Medicine, Dipeptidyl peptidase-4, Flavonoids, Pharmacology, SARS-CoV-2, business.industry, fungi, COVID-19, food and beverages, Inflammasome, General Medicine, medicine.disease, COVID-19 Drug Treatment, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Immunology, Therapeutics. Pharmacology, medicine.symptom, Signal transduction, Cytokine Release Syndrome, business, medicine.drug
Abstract

The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs) or bromodomain containing protein 4 (BRD4), and the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2), might be beneficial in regulating the cytokine storm during SARS-CoV-2 infection. Moreover, the ability of flavonoids to inhibit dipeptidyl peptidase 4 (DPP4), neutralize 3-chymotrypsin-like protease (3CLpro) or to affect gut microbiota to maintain immune response, and the dual action of angiotensin-converting enzyme 2 (ACE-2) may potentially also be applied to the exaggerated inflammatory responses induced by SARS-CoV-2. Based on the previously proven effects of flavonoids in other diseases or on the basis of newly published studies associated with COVID-19 (bioinformatics, molecular docking), it is reasonable to assume positive effects of flavonoids on inflammatory changes associated with COVID-19. This review highlights the current state of knowledge of the utility of flavonoids in the management of COVID-19 and also points to the multiple biological effects of flavonoids on signaling pathways associated with the inflammation processes that are deregulated in the pathology induced by SARS-CoV-2. The identification of agents, including naturally occurring substances such as flavonoids, represents great approach potentially utilizable in the management of COVID-19. Although not clinically investigated yet, the applicability of flavonoids against COVID-19 could be a promising strategy due to a broad spectrum of their biological activities., Graphical Abstract ga1

Published
2021
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45. Immunomodulatory effects of stem cells: Therapeutic option for neurodegenerative disorders

Author

Dario Siniscalco, Nazarii Kobyliak, Vanda Valentova, Nadezda Stollárová, Iveta Gasparova, Luis Rodrigo, Martin Caprnda, Dietrich Büsselberg, Jozef Dragasek, Robert Prosecky, Ioana Mozos, Peter Kubatka, Katarina Gazdikova, Giampiero La Rocca, Peter Kruzliak, Caprnda, M., Kubatka, P., Gazdikova, K., Gasparova, I., Valentova, V., Stollarova, N., LA ROCCA, G., Kobyliak, N., Dragasek, J., Mozos, I., Prosecky, R., Siniscalco, D., Busselberg, D., Rodrigo, L., and Kruzliak, P.

Subjects
0301 basic medicine, Settore BIO/17 - Istologia, Pathology, medicine.medical_specialty, medicine.medical_treatment, Regenerative medicine, Models, Biological, 03 medical and health sciences, medicine, Animals, Humans, Immunologic Factors, Induced pluripotent stem cell, Pharmacology, Stem cell therapy, business.industry, Multiple sclerosis, Stem Cells, Mesenchymal stem cell, Neurodegenerative Diseases, General Medicine, Stem-cell therapy, Neurodegenerative disorder, medicine.disease, Embryonic stem cell, Neural stem cell, 030104 developmental biology, Stem cell, business, Neuroscience, Stem Cell Transplantation
Abstract

Stem cells have the capability of self-renewal and can differentiate into different cell types that might be used in regenerative medicine. Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) currently lack effective treatments. Although stem cell therapy is still on the way from bench to bedside, we consider that it might provide new hope for patients suffering with neurodegenerative diseases. In this article, we will give an overview of recent studies on the potential therapeutic use of mesenchymal stem cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and perinatal stem cells to neurodegenerative disorders and we will describe their immunomodulatory mechanisms of action in specific therapeutic modalities.

Published
2017

46. Dietary natural products and their potential to influence health and disease including animal model studies

Author

Yeung, Andy Wai Kan, Aggarwal, Bharat Bhushan, Barreca, Davide, Battino, Maurizio, Belwal, Tarun, Horbanczuk, Olaf K., Berindan-Neagoe, Ioana, Bishayee, Anupam, Daglia, Maria, Devkota, Hari Prasad, Echeverria, Javier, El-Demerdash, Amr, Orhan, Ilkay Erdogan, Godfrey, Keith M., Gupta, Vijai Kumar, Horbanczuk, Jaroslaw O., Modlinski, Jacek A., Huber, Lukas A., Huminiecki, Lukasz, Artur Jóźwik, Marchewka, Joanna, Miller, Mark J. S., Mocan, Andrei, Mozos, Ioana, Nabavi, Seyed Fazel, Nabavi, Seyed Mohammad, Pieczynska, Magdalena D., Pittala, Valeria, Rengasamy, Kannan R. R., Silva, Ana Sanches, Sheridan, Helen, Stankiewicz, Adrian M., Strzalkowska, Nina, Sureda, Antoni, Tewari, Devesh, Weissig, Volkmar, Zengin, Gokhan, Atanasov, Atanas G., Yeung, A. W. K., Aggarwal, B. B., Barreca, D., Battino, M., Belwal, T., Horbanczuk, O. K., Berindan-Neagoe, I., Bishayee, A., Daglia, M., Devkota, H. P., Echeverria, J., El-Demerdash, A., Orhan, I. E., Godfrey, K. M., Gupta, V. K., Horbanczuk, J. O., Modlinski, J. A., Huber, L. A., Huminiecki, L., Jozwik, A., Marchewka, J., Miller, M. J. S., Mocan, A., Mozos, I., Nabavi, S. F., Nabavi, S. M., Pieczynska, M. D., Pittala, V., Rengasamy, K. R. R., Silva, A. S., Sheridan, H., Stankiewicz, A. M., Strzalkowska, N., Sureda, A., Tewari, D., Weissig, V., Zengin, G., and Atanasov, A. G.

Subjects
Natural products, Dietary, Animal models, Bioactive compounds, Citation analysis, Food science, Biotechnology, Animal Science and Zoology, Genetics, Veterinary (all), Citation analysi, Animal model, Bioactive compound, animal models, bioactive compounds, citation analysis, dietary, food science, natural products
Abstract

Although biological and pharmacological effects of dietary natural products have been intensively studied, there has been no bibliometric analysis performed on this research field up to now. The current study has aimed to identify and analyze the manuscripts on dietary natural products and their potential to influence health and disease including studies using animal models. Data, including words from titles and abstracts, publication and citation data, have been extracted from Web of Science database and analyzed by the VOSviewer software. Our search has yielded 1,014 manuscripts. The ratio of original articles to reviews was identified to be 1.5:1. Over half of the manuscripts have been published since 2010. The manuscripts have been contributed by 4,301 authors from 1,445 organizations in 76 countries/territories and published in 499 journals. The results from the current study point out that scientific research focusing on the potential of dietary natural products to affect health and disease status (including animal model studies) is expanding, and suggests an increasing significance of this scientific area. With the progressive development and improvement of animal studies, it should be expected that animal models of different human diseases (especially civilization ones) would be an integral part of the research for the evaluation of pharmaceuticals originated from dietary natural products like plants or plant materials. Moreover, natural products can also be fed to animals to improve the quality of animal products, with numerous resulting functional effects. © 2018, Polish Academy of Sciences. All rights reserved.

47. Poised PABP-RNA hubs implement signal-dependent mRNA decay in development.

Author

Modic M, Kuret K, Steinhauser S, Faraway R, van Genderen E, Ruiz de Los Mozos I, Novljan J, Vičič Ž, Lee FCY, Ten Berge D, Luscombe NM, and Ule J

Subjects
Animals, Mice, Signal Transduction, Humans, Poly(A)-Binding Proteins metabolism, Poly(A)-Binding Proteins genetics, Gene Expression Regulation, Developmental, Phosphorylation, RNA Stability, 3' Untranslated Regions genetics, RNA, Messenger metabolism, RNA, Messenger genetics, RNA-Binding Proteins metabolism, RNA-Binding Proteins genetics
Abstract

Signaling pathways drive cell fate transitions largely by changing gene expression. However, the mechanisms for rapid and selective transcriptome rewiring in response to signaling cues remain elusive. Here we use deep learning to deconvolve both the sequence determinants and the trans-acting regulators that trigger extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase kinase (MEK)-induced decay of the naive pluripotency mRNAs. Timing of decay is coupled to embryo implantation through ERK-MEK phosphorylation of LIN28A, which repositions pLIN28A to the highly A+U-rich 3' untranslated region (3'UTR) termini of naive pluripotency mRNAs. Interestingly, these A+U-rich 3'UTR termini serve as poly(A)-binding protein (PABP)-binding hubs, poised for signal-induced convergence with LIN28A. The multivalency of AUU motifs determines the efficacy of pLIN28A-PABP convergence, which enhances PABP 3'UTR binding, decreases the protection of poly(A) tails and activates mRNA decay to enable progression toward primed pluripotency. Thus, the signal-induced convergence of LIN28A with PABP-RNA hubs drives the rapid selection of naive mRNAs for decay, enabling the transcriptome remodeling that ensures swift developmental progression., (© 2024. The Author(s).)

Published
2024
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48. Gut microbiota produces biofilm-associated amyloids with potential for neurodegeneration.

Author

Fernández-Calvet A, Matilla-Cuenca L, Izco M, Navarro S, Serrano M, Ventura S, Blesa J, Herráiz M, Alkorta-Aranburu G, Galera S, Ruiz de Los Mozos I, Mansego ML, Toledo-Arana A, Alvarez-Erviti L, and Valle J

Subjects
Animals, Humans, Mice, Autophagy, Neurodegenerative Diseases metabolism, Mice, Inbred C57BL, Bacterial Proteins metabolism, Bacterial Proteins genetics, Brain metabolism, Brain pathology, Synucleinopathies metabolism, Synucleinopathies pathology, Gastrointestinal Microbiome, Caenorhabditis elegans metabolism, Caenorhabditis elegans microbiology, Biofilms growth & development, Amyloid metabolism, alpha-Synuclein metabolism, alpha-Synuclein genetics, Parkinson Disease metabolism, Parkinson Disease microbiology, Parkinson Disease pathology, Dopaminergic Neurons metabolism
Abstract

Age-related neurodegenerative diseases involving amyloid aggregation remain one of the biggest challenges of modern medicine. Alterations in the gastrointestinal microbiome play an active role in the aetiology of neurological disorders. Here, we dissect the amyloidogenic properties of biofilm-associated proteins (BAPs) of the gut microbiota and their implications for synucleinopathies. We demonstrate that BAPs are naturally assembled as amyloid-like fibrils in insoluble fractions isolated from the human gut microbiota. We show that BAP genes are part of the accessory genomes, revealing microbiome variability. Remarkably, the abundance of certain BAP genes in the gut microbiome is correlated with Parkinson's disease (PD) incidence. Using cultured dopaminergic neurons and Caenorhabditis elegans models, we report that BAP-derived amyloids induce α-synuclein aggregation. Our results show that the chaperone-mediated autophagy is compromised by BAP amyloids. Indeed, inoculation of BAP fibrils into the brains of wild-type mice promote key pathological features of PD. Therefore, our findings establish the use of BAP amyloids as potential targets and biomarkers of α-synucleinopathies., (© 2024. The Author(s).)

Published
2024
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49. Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions-A Review from the VascAgeNet COST Action.

Author

Pucci G, Grillo A, Dalakleidi KV, Fraenkel E, Gkaliagkousi E, Golemati S, Guala A, Hametner B, Lazaridis A, Mayer CC, Mozos I, Pereira T, Veerasingam D, Terentes-Printzios D, and Agnoletti D

Abstract

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field., Competing Interests: The authors declare no conflicts of interest.

Published
2024
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50. Procalcitonin kinetics following abdominal aortic surgery and its value for postoperative intestinal ischaemia detection.

Author

Novotny T, Staffa R, Tomandl J, Krivka T, Kruzliak P, Tomandlova M, Slaby O, Sponiar J, Caprnda M, Gaspar L, Rodrigo L, Mozos I, Kubicek L, Biros E, Vlachovsky R, Radova L, and Konieczna A

Subjects
Male, Humans, Female, Procalcitonin, Prospective Studies, Abdomen, Postoperative Period, Ischemia diagnostic imaging, Ischemia surgery, Atherosclerosis, Leriche Syndrome, Mesenteric Ischemia diagnostic imaging, Mesenteric Ischemia surgery
Abstract

Objective: The purpose of our study was to describe perioperative kinetics of procalcitonin (PCT) in patients undergoing aortic surgery, to compare the kinetics in the open abdominal aortic aneurysm (AAA) repair and aortobifemoral bypass for aortoiliac occlusive disease (AIOD), and to evaluate the ability of PCT to detect intestinal ischaemia., Methods: A prospective non-randomized observational cohort study in 80 patients (62 men and 18 women) undergoing elective aortic surgery was performed. Serum PCT was measured at baseline and defined intraoperative and postoperative timepoints up to postoperative day 7. MRI contrast-enhanced imaging was used to detect intestinal ischaemia., Results: The comparison of the AAA and AIOD cohort did not show any significant difference in PCT levels. Patients with intestinal ischaemia had higher serum PCT at multiple timepoints postoperatively. The most accurate timepoints for early diagnosis were postoperative day 3, followed by 24 h after declamping of the vascular reconstruction, and postoperative day 7. The sensitivity and negative predictive values were 100% in all mentioned timepoints. However, event at the best timepoint the specificity was 89% and the positive predictive value 43%., Conclusions: Procalcitonin levels in the postoperative period at proper timepoints might help to detect postoperative intestinal ischaemia. The limitation of this marker is its low specificity for intestinal ischaemia and low positive predictive value. The highest value of this marker is that it can rule out this complication because normal PCT levels mean that intestinal ischaemia is very unlikely., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Published
2023
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