125 results on '"De Chiara L"'
Search Results
2. WCN23-0619 TUBULAR CELL POLYPLOIDY PROTECTS FROM LETHAL ACUTE KIDNEY INJURY BUT PROMOTES CONSEQUENT CHRONIC KIDNEY DISEASE
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De Chiara, L., primary, Lazzeri, E., additional, and Romagnani, P., additional
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- 2023
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3. SARS-CoV-2 VARIANT PREVALENCE ESTIMATION USING WASTEWATER SAMPLES
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López-de-Ullibarri, I., primary, Tomás, L., additional, Trigo-Tasende, N., additional, Freire, B., additional, Vaamonde, M., additional, Gallego-García, P., additional, Barbeito, I., additional, Vallejo, J.A., additional, Tarrío-Saavedra, J., additional, Alvariño, P., additional, Beade, E., additional, Estévez, N., additional, Rumbo-Feal, S., additional, Conde-Pérez, K., additional, de Chiara, L., additional, Iglesias-Corrás, I., additional, Poza, M., additional, Ladra, S., additional, Posada, D., additional, and Cao, R., additional
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- 2023
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4. Efficiency comparison of Programmed SAID in investments in the distribution system
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Saldanha, T. M., primary, Boff, D. S., additional, Kirsch, I., additional, de Figueiredo, R. M., additional, da Silva Pereira, P. R., additional, and de Chiara, L. M., additional
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- 2023
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5. POS-067 TUBULAR CELL POLYPLOIDY IS LIFESAVING AFTER ACUTE KIDNEY INJURY AND A TARGET TO PREVENT CHRONIC KIDNEY DISEASE
- Author
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De Chiara, L., primary, Lazzeri, E., additional, and Romagnani, P., additional
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- 2022
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6. Spread of a SARS-CoV-2 variant through Europe in the summer of 2020
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Hodcroft E.B., Zuber M., Nadeau S., Vaughan T.G., Crawford K.H.D., Althaus C.L., Reichmuth M.L., Bowen J.E., Walls A.C., Corti D., Bloom J.D., Veesler D., Mateo D., Hernando A., Comas I., González-Candelas F., Goig G.A., Chiner-Oms Á., Cancino-Muñoz I., López M.G., Torres-Puente M., Gomez-Navarro I., Jiménez-Serrano S., Ruiz-Roldán L., Bracho M.A., García-González N., Martínez-Priego L., Galán-Vendrell I., Ruiz-Hueso P., De Marco G., Ferrús M.L., Carbó-Ramírez S., D’Auria G., Coscollá M., Ruiz-Rodríguez P., Roig-Sena F.J., Sanmartín I., Garcia-Souto D., Pequeno-Valtierra A., Tubio J.M.C., Rodríguez-Castro J., Rabella N., Navarro F., Miró E., Rodríguez-Iglesias M., Galán-Sanchez F., Rodriguez-Pallares S., de Toro M., Escudero M.B., Azcona-Gutiérrez J.M., Alberdi M.B., Mayor A., García-Basteiro A.L., Moncunill G., Dobaño C., Cisteró P., García-de-Viedma D., Pérez-Lago L., Herranz M., Sicilia J., Catalán-Alonso P., Muñoz P., Muñoz-Cuevas C., Rodríguez-Rodríguez G., Alberola-Enguidanos J., Nogueira J.M., Camarena J.J., Rezusta A., Tristancho-Baró A., Milagro A., Martínez-Cameo N.F., Gracia-Grataloup Y., Martró E., Bordoy A.E., Not A., Antuori-Torres A., Benito R., Algarate S., Bueno J., del Pozo J.L., Boga J.A., Castelló-Abietar C., Rojo-Alba S., Alvarez-Argüelles M.E., Melon S., Aranzamendi-Zaldumbide M., Vergara-Gómez A., Fernández-Pinero J., Martínez M.J., Vila J., Rubio E., Peiró-Mestres A., Navero-Castillejos J., Posada D., Valverde D., Estévez-Gómez N., Fernandez-Silva I., de Chiara L., Gallego-García P., Varela N., Moreno R., Tirado M.D., Gomez-Pinedo U., Gozalo-Margüello M., Eliecer-Cano M., Méndez-Legaza J.M., Rodríguez-Lozano J., Siller M., Pablo-Marcos D., Oliver A., Reina J., López-Causapé C., Canut-Blasco A., Hernáez-Crespo S., Cordón M.L.A., Lecároz-Agara M.-C., Gómez-González C., Aguirre-Quiñonero A., López-Mirones J.I., Fernández-Torres M., Almela-Ferrer M.R., Gonzalo-Jiménez N., Ruiz-García M.M., Galiana A., Sanchez-Almendro J., Cilla G., Montes M., Piñeiro L., Sorarrain A., Marimón J.M., Gomez-Ruiz M.D., López-Hontangas J.L., González Barberá E.M., Navarro-Marí J.M., Pedrosa-Corral I., Sanbonmatsu-Gámez S., Pérez-González C., Chamizo-López F., Bordes-Benítez A., Navarro D., Albert E., Torres I., Gascón I., Torregrosa-Hetland C.J., Pastor-Boix E., Cascales-Ramos P., Fuster-Escrivá B., Gimeno-Cardona C., Ocete M.D., Medina-Gonzalez R., González-Cantó J., Martínez-Macias O., Palop-Borrás B., de Toro I., Mediavilla-Gradolph M.C., Pérez-Ruiz M., González-Recio Ó., Gutiérrez-Rivas M., Simarro-Córdoba E., Lozano-Serra J., Robles-Fonseca L., de Salazar A., Viñuela-González L., Chueca N., García F., Gómez-Camarasa C., Carvajal A., de la Puente R., Martín-Sánchez V., Fregeneda-Grandes J.-M., Molina A.J., Argüello H., Fernández-Villa T., Farga-Martí M.A., Domínguez-Márquez V., Costa-Alcalde J.J., Trastoy R., Barbeito-Castiñeiras G., Coira A., Pérez-del-Molino M.L., Aguilera A., Planas A.M., Soriano A., Fernandez-Cádenas I., Pérez-Tur J., Marcos M.Á., Moreno-Docón A., Viedma E., Mingorance J., Galán-Montemayor J.C., Parra-Grande M., Stadler T., Neher R.A., Swiss National Science Foundation, European Commission, University of Basel, ETH Zurich, National Institute of General Medical Sciences (US), National Institute of Allergy and Infectious Diseases (US), Burroughs Wellcome Fund, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Howard Hughes Medical Institute, Hodcroft, Emma B. [0000-0002-0078-2212], Zuber, Moira [0000-0002-4275-8739], Nadeau, Sarah [0000-0003-1008-8918], Vaughan, Timothy G. [0000-0001-6220-2239], Crawford, Katharine H. D. [0000-0002-6223-4019], Althaus, Christian L. [0000-0002-5230-6760], Reichmuth, Martina L. [0000-0001-9345-851X], Bowen, John E. [0000-0003-3590-9727], Walls, Alexandra C. [0000-0002-9636-8330], Corti, Davide [0000-0002-5797-1364], Bloom, Jesse D. [0000-0003-1267-3408], Veesler, David [0000-0002-6019-8675], Mateo, David [0000-0002-1590-4163], Hernando de Castro, Alberto [0000-0003-1180-1068], Comas, Iñaki [0000-0001-5504-9408], González-Candelas, Fernando [0000-0002-0879-5798], Stadler, Tanja [0000-0001-6431-535X], Neher, Richard A. [0000-0003-2525-1407], Hodcroft, Emma B., Zuber, Moira, Nadeau, Sarah, Vaughan, Timothy G., Crawford, Katharine H. D., Althaus, Christian L., Reichmuth, Martina L., Bowen, John E., Walls, Alexandra C., Corti, Davide, Bloom, Jesse D., Veesler, David, Mateo, David, Hernando de Castro, Alberto, Comas, Iñaki, González-Candelas, Fernando, Stadler, Tanja, and Neher, Richard A.
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Phylogenetics ,Sars-Cov-2 ,Viral infection ,0303 health sciences ,2019-20 coronavirus outbreak ,Multidisciplinary ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,610 Medicine & health ,3. Good health ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Transmission (mechanics) ,Geography ,360 Social problems & social services ,law ,Development economics ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Following its emergence in late 2019, the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2 has been tracked via phylogenetic analysis of viral genome sequences in unprecedented detail3–5. While the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, within Europe travel resumed in the summer of 2020. Here we report on a novel SARS-CoV-2 variant, 20E (EU1), that emerged in Spain in early summer, and subsequently spread across Europe. We find no evidence of increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate 20E (EU1) was introduced hundreds of times to European countries by summertime travelers, likely undermining local efforts to keep SARS-CoV-2 cases low. Our results demonstrate how a variant can rapidly become dominant even in absence of a substantial transmission advantage in favorable epidemiological settings. Genomic surveillance is critical to understanding how travel can impact SARS-CoV-2 transmission, and thus for informing future containment strategies as travel resumes., This work was supported by the Swiss National Science Foundation (SNSF) through grant numbers 31CA30 196046 (to RAN, EBH, CLA), 31CA30 196267 (to TS), European Union’s Horizon 2020 research and innovation programme - project EpiPose (No 101003688) (MLR, CLA), core funding by the University of Basel and ETH Zürich, the National Institute of General Medical Sciences (R01GM120553 to DV), the National Institute of Allergy and Infectious Diseases (DP1AI158186 and HHSN272201700059C to DV), a Pew Biomedical Scholars Award (DV), an Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund (DV and JDB), a Fast Grants (DV), and NIAID grants R01AI141707 (JDB) and F30AI149928 (KHDC). SeqCOVID-SPAIN is funded by the Instituto de Salud Carlos III project COV20/00140, Spanish National Research Council and ERC StG 638553 to IC and BFU2017-89594R from MICIN to FGC. JDB is an Investigator of the Howard Hughes Medical Institute.
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- 2021
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7. DATA MINING APPLIED TO FEATURES SELECTIVITY FOR A NON-TECHNICAL LOSS DETECTION MODEL IN RURAL DISTRIBUTION GRIDS
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Uberti, V., primary, Bernardon, D. P., additional, Vieira, V., additional, Heinke, M., additional, De Figueiredo, R., additional, Evaldt, M., additional, Abaide, A., additional, de Chiara, L., additional, and Silva, J. A., additional
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- 2021
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8. Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells
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Antonelli, G, Angelotti, Ml, Allinovi, M, Guzzi, F, Sisti, A, Semeraro, R, Conte, C, Mazzinghi, B, Nardi, S, Melica, Me, De Chiara, L, Lazzeri, E, Lasagni, L, Lottini, T, Landini, S, Giglio, S, Mari, A, Di Maida, F, Antonelli, A, Porpiglia, F, Schiavina, R, Ficarra, V, Facchiano, D, Gacci, M, Serni, S, Carini, M, Netto, Gj, Roperto, Rm, Magi, A, Christiansen, Cf, Rotondi, M, Liapis, H, Anders, Hj, Minervini, A, Raspollini, Mr, and Romagnani, P.
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Acute kidney injury, renal cell carcinoma, renal progenitors - Published
- 2020
9. DNA methylation as an additional diagnostic tool for tumoral mediastinal lymph nodes in non-small cell lung cancer: P21-83
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De Chiara, L., Leiro-Fernández, V., Botana-Rial, M. I., Represas-Represas, C., Valverde, D., and Villar, A. F.
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- 2012
10. Early clinical predictors and correlates of long-term morbidity in bipolar disorder
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Serra, G., primary, Koukopoulos, A, additional, De Chiara, L., additional, Koukopoulos, A.E., additional, Sani, G., additional, Tondo, L., additional, Girardi, P., additional, Reginaldi, D., additional, and Baldessarini, R.J., additional
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- 2017
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11. Pediatric Mania: The Controversy Between Euphoria and Irritability
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Serra, G., primary, Uchida, M., additional, Battaglia, C., additional, Casini, M.P., additional, De Chiara, L., additional, Biederman, J., additional, Vicari, S., additional, and Wozniak, J., additional
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- 2017
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12. Memantine in the treatment and prophylaxis of bipolar type II mood disorder and co-morbid eating disorder. a case report [Memantina nel trattamento e nella profilassi del disturbo dell’umore bipolare di tipo II in comorbilità con disturbo del comportamento alimentare. un caso clinico]
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De Chiara, L, Serra, G, and Koukopoulos, A
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memantine ,bipolar type II mood disorder ,eating disorder - Published
- 2014
13. Differentiation plasticity of germline cell-derived pluripotent stem cells and their potential application in regenerative medicine
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Fagoonee S, De Chiara L, Silengo L, and Altruda F
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Embryonic stem cells ,iPS ,food and beverages ,regenerative medicine ,Spermatogonial stem cells ,differentiation - Abstract
Pluripotent stem cells hold the key to replacing cells lost in many degenerative diseases. Stem cells can be differentiated into specialized cell types and can be a useful source of healthy cells in genetic disease, especially those which can be corrected by only a small amount of functional protein. In the last years impressive efforts have been made in understanding the potential application of pluripotent stem cells in the field of regenerative medicine. In these review, we will discuss the differentiation plasticity of mouse Germline Cell-derived Pluripotent Stem Cells (GPSCs) into different cell types with the aim to translating these potentialities to human organ regeneration.
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- 2014
14. Piezosurgery vs High Speed Rotary Handpiece: a comparison between the two techniques in the impacted third molar surgery
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Bartuli, F, Luciani, F, Caddeo, F, De Chiara, L, Piva, P, Ottria, L, and Arcuri, C
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Settore MED/28 - Malattie Odontostomatologiche - Published
- 2013
15. Serum sCD26 for colorectal cancer screening in family-risk individuals: comparison with faecal immunochemical test
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Otero-Estévez, O, primary, De Chiara, L, additional, Rodríguez-Berrocal, F J, additional, de la Cadena, M Páez, additional, Cubiella, J, additional, Castro, I, additional, Gonzalez-Mao, C, additional, Hernandez, V, additional, and Martínez-Zorzano, V S, additional
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- 2014
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16. Atypical prodromal onset in affective disorders
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Serra, G, primary, Manfredi, G, additional, Faedda, G, additional, De Chiara, L, additional, Sani, G, additional, Koukopoulos, A, additional, and Girardi, P, additional
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- 2012
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17. Serum sCD26 for colorectal cancer screening in family-risk individuals: comparison with faecal immunochemical test.
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Otero-Estévez, O, De Chiara, L, Rodríguez-Berrocal, F J, de la Cadena, M Páez, Cubiella, J, Castro, I, Gonzalez-Mao, C, Hernandez, V, and Martínez-Zorzano, V S
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CD26 antigen , *COLON cancer diagnosis , *IMMUNOCHEMISTRY , *BIOMARKERS , *COLONOSCOPY - Abstract
Background:The development of specific screening programs for individuals with a family history of colorectal cancer (CRC) is a priority. This study evaluates the diagnostic performance of serum soluble CD26 (sCD26) in family-risk individuals and compares this marker with the faecal immunochemical test for the detection of advanced neoplasia (AN) (CRC or advanced adenomas; AA).Methods:Five hundred and sixteen asymptomatic individuals with at least one first-degree relative with CRC were included. Serum sCD26 was measured in all the individuals who also underwent a colonoscopy (53 AA and four cancer cases were found) and a faecal immunochemical test.Results:Setting specificity to 90% and 95%, respectively, sCD26 showed a sensitivity of 39.6% and 28.3% for AA, and of 42.1% and 28.1% for AN. The combination of sCD26 and the faecal test detected AA and AN with a 52.8% and 56.1% sensitivity, corresponding to 93.5% specificity.Conclusions:The combination of serum sCD26 and the faecal blood test could result a valuable strategy for detecting AN in familial-risk CRC screening. [ABSTRACT FROM AUTHOR]
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- 2015
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18. PIEZOSURGERY VS HIGH SPEED ROTARY HANDPIECE: A COMPARISON BETWEEN THE TWO TECHNIQUES IN THE IMPACTED THIRD MOLAR SURGERY.
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BARTULI, F. N., LUCIANI, F., CADDEO, F., DE CHIARA, L., DI DIO, M., PIVA, P., OTTRIA, L., and ARCURI, C.
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DENTAL extraction ,TEETH surgery ,MOLARS ,SURGERY ,ANALGESICS ,PAIN management - Abstract
Objective. The aim of the Study was to compare the impacted third molar surgical technique by means of the high speed rotary handpiece with the piezoelectric one. Materials and Methods. 192 patients have been selected among those who had to undergo a third molar surgical extraction. These patients' surgeries have been performed by means of one of the techniques, randomly chosen. Each patient has undergone the same analgesic therapy (paracetamol 1000 mg tablets). Each surgery has been performed by the same surgeon. The patients were asked to fill in a questionnaire concerning the postoperative pain ("happy face pain" rating scale). Results. The average duration of the surgeries performed by means of the high speed rotary handpiece was 32 minutes, while the duration of the ones performed by means of the piezoelectric handpiece was much longer (54 minutes). The postoperative pain values were almost equal. Conclusions. In conclusion, the osteotomy performed by means of the traditional technique still represents the gold standard in the impacted third molar surgery. The piezoelectric technique may be an effective choice, especially for the less skilled surgeons, in order to guarantee the protection of the delicate locoregional anatomical structures. [ABSTRACT FROM AUTHOR]
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- 2013
19. Characterization of cyclic AMP phosphodiesterases in Leishmania mexicana and purification of a soluble form
- Author
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Rascon, A., Viloria, M. E., De-Chiara, L., and Dubra, M. E.
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- 2000
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20. STUDI SPERIMENTALI E CLINICI NELLE SUPERINFEZIONI DA PSEUDOMONAS AERUGINOSA
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AURILIO, Caterina, GRELLA A, BARBAGALLO A, DEQUERQUIS S, DE CHIARA L, ARGENZIO F., Aurilio, Caterina, Grella, A, Barbagallo, A, Dequerquis, S, DE CHIARA, L, and Argenzio, F.
- Published
- 1977
21. SUPERINFEZIONE DA PS. AERUGINOSA NELLA RIANIMAZIONE CARDIOCHIRURGICA
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BARBAGALLO A, DEQUERQUIS S, DE CHIARA L, GRELLA A, ARGENZIO F., AURILIO, Caterina, Barbagallo, A, Dequerquis, S, DE CHIARA, L, Grella, A, Aurilio, Caterina, and Argenzio, F.
- Published
- 1977
22. miR302 regulates SNAI1 expression to control mesangial cell plasticity.
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De Chiara, L., Andrews, D., Watson, A., Oliviero, G., Cagney, G., and Crean, J.
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Cell fate decisions are controlled by the interplay of transcription factors and epigenetic modifiers, which together determine cellular identity. Here we elaborate on the role of miR302 in the regulation of cell plasticity. Overexpression of miR302 effected silencing of the TGFβ type II receptor and facilitated plasticity in a manner distinct from pluripotency, characterized by increased expression of Snail. miR302 overexpressing mesangial cells also exhibited enhanced expression of EZH2 coincident with Snail upregulation. esiRNA silencing of each component suggest that Smad3 and EZH2 are part of a complex that regulates plasticity and that miR302 regulates EZH2 and Snail independently. Subsequent manipulation of miR302 overexpressing cells demonstrated the potential of using this approach for reprogramming as evidenced by de novo expression of the tight junction components ZO-1 and E-cadherin and the formation of ZO-1 containing tight junctions. Understanding the processes through which dynamic epigenetic silencing is controlled in adults cells will allow us to address the epigenetic state of acquired disease and whether original states, regenerative in nature, can be restored with therapy. [ABSTRACT FROM AUTHOR]
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- 2017
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23. Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas
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Páez de la Cadena María, Martínez-Ares David, Cordero Oscar J, Rodríguez-Berrocal Francisco J, Rodríguez-Piñeiro Ana M, and De Chiara Loretta
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Serum CD26 (sCD26) levels were previously found diminished in colorectal cancer (CRC) patients compared to healthy donors, suggesting its potential utility for early diagnosis. Therefore we aimed to estimate the utility of the sCD26 as a biomarker for CRC and advanced adenomas in a high-risk group of patients. The relationship of this molecule with polyp characteristics was also addressed. Methods sCD26 levels were measured by ELISA in 299 symptomatic and asymptomatic patients who had undergone a colonoscopy. Patients were diagnosed as having no colorectal pathology, non-inflammatory or inflammatory bowel disease, polyps (hyperplastic, non-advanced and advanced adenomas) or CRC. Results At a 460 ng/mL cut-off, the sCD26 has a sensitivity and specificity of 81.8% (95% CI, 64.5-93.0%) and 72.3% (95% CI, 65.0-77.2%) for CRC regarding no or benign colorectal pathology. Clinicopathological analysis of polyps showed a relationship between the sCD26 and the grade of dysplasia and the presence of advanced adenomas. Hence, a 58.0% (95% CI, 46.5-68.9%) sensitivity detecting CRC and advanced adenomas was obtained, with a specificity of 75.5% (95% CI, 68.5-81.0%). Conclusions Our preliminary results show that measurement of the sCD26 is a non-invasive and reasonably sensitive assay, which could be combined with others such as the faecal occult blood test for the early diagnosis and screening of CRC and advanced adenomas. Additional comparative studies in average-risk populations are necessary.
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- 2010
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24. Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells
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Hans-Joachim Anders, Alessandro Antonelli, Tiziano Lottini, Andrea Minervini, Marco Carini, Francesco Guzzi, Paola Romagnani, Mauro Gacci, Alessandro Sisti, Carolina Conte, Fabrizio Di Maida, Mario Rotondi, Samuela Landini, Marco Allinovi, Maria Elena Melica, Rosa Maria Roperto, Francesco Porpiglia, Vincenzo Ficarra, Benedetta Mazzinghi, Sergio Serni, Sabrina Giglio, George J. Netto, Maria Rosaria Raspollini, Maria Lucia Angelotti, Letizia De Chiara, Sara Nardi, Giulia Antonelli, Davide Facchiano, Alberto Magi, Riccardo Schiavina, Elena Lazzeri, Helen Liapis, Andrea Mari, Roberto Semeraro, Christian Fynbo Christiansen, Laura Lasagni, Anna Julie Peired, Peired A.J., Antonelli G., Angelotti M.L., Allinovi M., Guzzi F., Sisti A., Semeraro R., Conte C., Mazzinghi B., Nardi S., Melica M.E., De Chiara L., Lazzeri E., Lasagni L., Lottini T., Landini S., Giglio S., Mari A., Di Maida F., Antonelli A., Porpiglia F., Schiavina R., Ficarra V., Facchiano D., Gacci M., Serni S., Carini M., Netto G.J., Roperto R.M., Magi A., Christiansen C.F., Rotondi M., Liapis H., Anders H.-J., Minervini A., Raspollini M.R., and Romagnani P.
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Adenoma ,0301 basic medicine ,papillary renal cell carcinoma ,medicine.disease_cause ,urologic and male genital diseases ,DISEASE ,PATHWAY ,PROTECTS ,Mice ,03 medical and health sciences ,0302 clinical medicine ,AKI ,NOTCH1 ,REGENERATION ,Renal cell carcinoma ,Biomarkers, Tumor ,ABLATION ,medicine ,Carcinoma ,Animals ,Progenitor cell ,RECURRENCE ,Carcinoma, Renal Cell ,RECEPTOR ,Papillary renal cell carcinomas ,business.industry ,Stem Cells ,Papillary Adenoma ,Acute kidney injury ,renal carcinoma ,General Medicine ,Acute Kidney Injury ,medicine.disease ,TUMORS ,Kidney Neoplasms ,3. Good health ,NOTCH ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,GROWTH ,Neoplasm Recurrence, Local ,Stem cell ,Carcinogenesis ,business - Abstract
Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression in human pRCC associated with worse outcome and was specific for type 2 pRCC. Mice overexpressing NOTCH1 in TECs developed papillary adenomas and type 2 pRCCs, and AKI accelerated this process. Lineage tracing in mice identified single renal progenitors as the cell of origin of papillary tumors. Single-cell RNA sequencing showed that human renal progenitor transcriptome showed similarities to PT1, the putative cell of origin of human pRCC. Furthermore, NOTCH1 overexpression in cultured human renal progenitor cells induced tumor-like 3D growth. Thus, AKI can drive tumorigenesis from local tissue progenitor cells. In particular, we find that AKI promotes the development of pRCC from single progenitors through a classical adenoma-carcinoma sequence.
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25. Inhibition of complement factor C5a or C5aR for cholesterol crystal embolism-related vascular thrombosis with microvascular injury and its consequences.
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Zhao D, Han C, Mammadova-Bach E, Watanabe-Kusunoki K, Bandeira Honda TS, Li Y, Li C, Li Q, Long H, Lyubenov L, Shi C, Santovito D, Weber C, Boor P, Droste P, Parikh S, Shapiro J, De Chiara L, Carangelo G, Romagnani P, Klussmann S, Vater A, and Anders HJ
- Abstract
Cholesterol crystal embolism (CCE) implies immunothrombosis, tissue necrosis, and organ failure but no specific treatments are available. As CCE involves complement activation, we speculated that inhibitors of the C5a/C5aR axis would be sufficient to attenuate the consequences of CCE like that with systemic vasculitis. Cholesterol microcrystal injection into the kidney artery of wild-type mice initiated intra-kidney immunothrombosis within a few hours followed by a sudden drop of glomerular filtration rate and ischemic kidney necrosis after 24 hours. Genetic deficiency of either C3 or C5aR prevented immunothrombosis, glomerular filtration rate drop, and ischemic necrosis at 24 hours as did preemptive treatment with inhibitors of either C5a or C5aR. Delayed C5a blockade after crystal injection still resolved crystal clots and prevented all consequences. Thus, selective blockade of C5a or C5aR is sufficient to attenuate the consequences of established CCE and prospective inhibition in high-risk patients may be clinically feasible and safe., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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26. Climate Change, Kidney Health, and Environmentally Sustainable Kidney Care: A Multinational Survey of Health Care Professionals.
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Sandal S, Ethier I, Onu U, Fung W, Bajpai D, Bilchut WH, Bagasha P, De Chiara L, Hafiz E, Smyth B, Kelly D, Pippias M, and Jha V
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- Humans, Health Personnel, Kidney Diseases therapy, Kidney Diseases epidemiology, Surveys and Questionnaires, Male, Female, Climate Change
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- 2024
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27. Dispersal history of SARS-CoV-2 in Galicia, Spain.
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Gallego-García P, Estévez-Gómez N, De Chiara L, Alvariño P, Juiz-González PM, Torres-Beceiro I, Poza M, Vallejo JA, Rumbo-Feal S, Conde-Pérez K, Aja-Macaya P, Ladra S, Moreno-Flores A, Gude-González MJ, Coira A, Aguilera A, Costa-Alcalde JJ, Trastoy R, Barbeito-Castiñeiras G, García-Souto D, Tubio JMC, Trigo-Daporta M, Camacho-Zamora P, Costa JG, González-Domínguez M, Canoura-Fernández L, Glez-Peña D, Pérez-Castro S, Cabrera JJ, Daviña-Núñez C, Godoy-Diz M, Treinta-Álvarez AB, Veiga MI, Sousa JC, Osório NS, Comas I, González-Candelas F, Hong SL, Bollen N, Dellicour S, Baele G, Suchard MA, Lemey P, Agulla A, Bou G, Alonso-García P, Pérez-Del-Molino ML, García-Campello M, Paz-Vidal I, Regueiro B, and Posada D
- Subjects
- Spain epidemiology, Humans, Genome, Viral, Phylogeny, Pandemics, COVID-19 epidemiology, COVID-19 transmission, COVID-19 virology, SARS-CoV-2 genetics
- Abstract
The dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron-BA.1 variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the United States became increasingly significant. The number of detected introductions varied from 96 and 101 for Alpha and Delta to 39 for Omicron-BA.1. Most of these introductions left a low number of descendants (<10), suggesting a limited impact on the evolution of the pandemic in Galicia. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)
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- 2024
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28. Is Antipsychotic Drug Use During Pregnancy Associated with Increased Malformation Rates and Worsening of Maternal and Infant Outcomes? A Systematic Review.
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Sani G, Callovini T, Ferrara OM, Segatori D, Margoni S, Simonetti A, Lisci FM, Marano G, Fischetti A, Kotzalidis GD, Di Segni F, Fiaschè F, Janiri D, Moccia L, Manfredi G, Alcibiade A, Brisi C, Grisoni F, Stella G, Bernardi E, Brugnami A, Ciliberto M, Spera MC, Caso R, Rossi S, Boggio G, Mastroeni G, Abate F, Conte E, Quintano A, De Chiara L, Monti L, Camardese G, Rinaldi L, Koukopoulos AE, Chieffo DPR, Angeletti G, and Mazza M
- Abstract
There is much debate about continuing antipsychotic medication in patients who need it when they become pregnant because benefits must be weighed against potential teratogenic and malformation effects related to antipsychotics themselves. To address this, we conducted a systematic review on the PubMed, PsycINFO and CINHAL databases and the ClinicalTrials.gov register using the following strategy: (toxicity OR teratogenicity OR malformation* OR "birth defect*" OR "congenital abnormality" OR "congenital abnormalities" OR "brain changes" OR "behavioral abnormalities" OR "behavioral abnormalities") AND antipsychotic* AND (pregnancy OR pregnant OR lactation OR delivery OR prenatal OR perinatal OR post-natal OR puerperium) on September 27, 2023. We found 38 studies to be eligible. The oldest was published in 1976, while most articles were recent. Most studies concluded that the antipsychotics, especially the second-generation antipsychotics, were devoid of teratogenic potential, while few studies were inconclusive and recommended replication. Most authoritative articles were from the Boston area, where large databases were implemented to study the malformation potential of psychiatric drugs. Other reliable databases are from Northern European registers. Overall conclusions are that antipsychotics are no more related to malformations than the disorders themselves; most studies recommend that there are no reasons to discontinue antipsychotic medications in pregnancy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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29. Capacity for the management of kidney failure in the International Society of Nephrology Western Europe region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).
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Pippias M, Alfano G, Kelly DM, Soler MJ, De Chiara L, Olanrewaju TO, Arruebo S, Bello AK, Caskey FJ, Damster S, Donner JA, Jha V, Johnson DW, Levin A, Malik C, Nangaku M, Okpechi IG, Tonelli M, Ye F, Coppo R, and Lightstone L
- Abstract
Western Europe boasts advanced health care systems, robust kidney care guidelines, and a well-established health care workforce. Despite this, significant disparities in kidney replacement therapy incidence, prevalence, and transplant access exist. This paper presents the third International Society of Nephrology Global Kidney Health Atlas's findings on kidney care availability, accessibility, affordability, and quality in 22 Western European countries, representing 99% of the region's population. The known chronic kidney disease (CKD) prevalence across Western Europe averages 10.6%, slightly above the global median. Cardiovascular diseases account for a substantial portion of CKD-related deaths. Kidney failure incidence varies. Government health expenditure differs; however, most countries offer government-funded acute kidney injury, dialysis, and kidney transplantation care. Hemodialysis and peritoneal dialysis are universally available, with variations in the number of dialysis centers. Kidney transplantation is available in all countries (except for 3 microstates), with variable transplant center prevalence. Conservative kidney management (CKM) is increasingly accessible. The region's kidney care workforce is substantial, exceeding global averages; however, workforce shortages are reported. Barriers to optimal kidney care include limited workforce capacity, lack of surveillance mechanisms, and suboptimal integration into national noncommunicable disease (NCD) strategies. Policy recognition of CKD as a health priority varies across countries. Although Western Europe exhibits strong kidney care infrastructure, opportunities for improvement exist, particularly in CKD prevention, surveillance, awareness, and policy implementation. Efforts to improve CKD care should include automated detection, educational support, and enhanced workflows. Based on these findings, health care professionals, stakeholders, and policymakers are called to act to enhance kidney care across the region., (© 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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30. Polyploid tubular cells: a shortcut to stress adaptation.
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De Chiara L, Lazzeri E, and Romagnani P
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- Animals, Cell Differentiation, Polyploidy, Kidney, Mammals, Hepatocytes, Epithelial Cells
- Abstract
Tubular epithelial cells (TCs) compose the majority of kidney parenchyma and play fundamental roles in maintaining homeostasis. Like other tissues, mostly immature TC with progenitor capabilities are able to replace TC lost during injury via clonal expansion and differentiation. In contrast, differentiated TC lack this capacity. However, as the kidney is frequently exposed to toxic injuries, evolution positively selected a response program that endows differentiated TC to maintain residual kidney function during kidney injury. Recently, we and others have described polyploidization of differentiated TC, a mechanism to augment the function of remnant TC after injury by rapid hypertrophy. Polyploidy is a condition characterized by >2 complete sets of chromosomes. Polyploid cells often display an increased functional capacity and are generally more resilient to stress as evidenced by being conserved across many plants and eukaryote species from flies to mammals. Here, we discuss the occurrence of TC polyploidy in different contexts and conditions and how this integrates into existing concepts of kidney cell responses to injury. Collectively, we aim at stimulating the acquisition of novel knowledge in the kidney field as well as accelerating the translation of this basic response mechanism to the clinical sphere., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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31. Green nephrology: an editor's journey.
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De Chiara L, Ronco P, and Rovin BH
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- Humans, Publishing, Nephrology
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- 2024
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32. Serum DNA methylome of the colorectal cancer serrated pathway enables non-invasive detection.
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Gallardo-Gómez M, Costas-Ríos L, Garcia-Prieto CA, Álvarez-Rodríguez L, Bujanda L, Barrero M, Castells A, Balaguer F, Jover R, Esteller M, Tardío Baiges A, González-Carreró Fojón J, Cubiella J, and De Chiara L
- Abstract
The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell-free DNA (cfDNA) methylomes as a potential source of biomarkers for the non-invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high-risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway-specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate-rich 1 (ERICH1) methylation discriminated high-risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non-invasive detection of colorectal serrated lesions., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
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- 2023
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33. Serum methylation of GALNT9, UPF3A, WARS, and LDB2 as noninvasive biomarkers for the early detection of colorectal cancer and advanced adenomas.
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Gallardo-Gómez M, Rodríguez-Girondo M, Planell N, Moran S, Bujanda L, Etxart A, Castells A, Balaguer F, Jover R, Esteller M, Cubiella J, Gómez-Cabrero D, and De Chiara L
- Subjects
- Humans, DNA Methylation, Early Detection of Cancer methods, Sensitivity and Specificity, Biomarkers, Tumor, Septins genetics, RNA-Binding Proteins genetics, Transcription Factors genetics, LIM Domain Proteins genetics, Cell-Free Nucleic Acids, Colorectal Neoplasms diagnosis, Colorectal Neoplasms genetics, Adenoma diagnosis, Adenoma genetics
- Abstract
Background: Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicenter cohort of 433 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC., Results: First, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new noninvasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test., Conclusions: Overall, this study highlights the utility of cfDNA methylation for CRC screening. Our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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34. Polyploid tubular cells initiate a TGF-β1 controlled loop that sustains polyploidization and fibrosis after acute kidney injury.
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De Chiara L, Semeraro R, Mazzinghi B, Landini S, Molli A, Antonelli G, Angelotti ML, Melica ME, Maggi L, Conte C, Peired AJ, Cirillo L, Raglianti V, Magi A, Annunziato F, Romagnani P, and Lazzeri E
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- Animals, Mice, Epithelial Cells, Polyploidy, Fibrosis, Transforming Growth Factor beta1 genetics, Acute Kidney Injury genetics
- Abstract
Polyploidization of tubular cells (TC) is triggered by acute kidney injury (AKI) to allow survival in the early phase after AKI, but in the long run promotes fibrosis and AKI-chronic kidney disease (CKD) transition. The molecular mechanism governing the link between polyploid TC and kidney fibrosis remains to be clarified. In this study, we demonstrate that immediately after AKI, expression of cell cycle markers mostly identifies a population of DNA-damaged polyploid TC. Using transgenic mouse models and single-cell RNA sequencing we show that, unlike diploid TC, polyploid TC accumulate DNA damage and survive, eventually resting in the G1 phase of the cell cycle. In vivo and in vitro single-cell RNA sequencing along with sorting of polyploid TC shows that these cells acquire a profibrotic phenotype culminating in transforming growth factor (TGF)-β1 expression and that TGF-β1 directly promotes polyploidization. This demonstrates that TC polyploidization is a self-sustained mechanism. Interactome analysis by single-cell RNA sequencing revealed that TGF-β1 signaling fosters a reciprocal activation loop among polyploid TC, macrophages, and fibroblasts to sustain kidney fibrosis and promote CKD progression. Collectively, this study contributes to the ongoing revision of the paradigm of kidney tubule response to AKI, supporting the existence of a tubulointerstitial cross talk mediated by TGF-β1 signaling produced by polyploid TC following DNA damage. NEW & NOTEWORTHY Polyploidization in tubular epithelial cells has been neglected until recently. Here, we showed that polyploidization is a self-sustained mechanism that plays an important role during chronic kidney disease development, proving the existence of a cross talk between infiltrating cells and polyploid tubular cells. This study contributes to the ongoing revision of kidney adaptation to injury, posing polyploid tubular cells at the center of the process.
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- 2023
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35. Tubuloid as an alternative model of ADPKD.
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Xia Y, De Chiara L, and Drummond IA
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- Humans, Mutation, TRPP Cation Channels genetics, Polycystic Kidney, Autosomal Dominant genetics
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- 2023
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36. No NLRP3 inflammasome activity in kidney epithelial cells, not even when the NLRP3-A350V Muckle-Wells variant is expressed in podocytes of diabetic mice.
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Kunte SC, Marschner JA, Klaus M, Honda T, Li C, Motrapu M, Walz C, Angelotti ML, Antonelli G, Melica ME, De Chiara L, Semeraro R, Nelson PJ, and Anders HJ
- Subjects
- Animals, Humans, Mice, Butyrates, Epithelial Cells, Inflammasomes, Interleukin-18, Kidney, Cryopyrin-Associated Periodic Syndromes, Diabetes Mellitus, Experimental, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Podocytes
- Abstract
Background: The NLRP3 inflammasome integrates several danger signals into the activation of innate immunity and inflammation by secreting IL-1β and IL-18. Most published data relate to the NLRP3 inflammasome in immune cells, but some reports claim similar roles in parenchymal, namely epithelial, cells. For example, podocytes, epithelial cells critical for the maintenance of kidney filtration, have been reported to express NLRP3 and to release IL-β in diabetic kidney disease, contributing to filtration barrier dysfunction and kidney injury. We questioned this and hence performed independent verification experiments., Methods: We studied the expression of inflammasome components in human and mouse kidneys and human podocytes using single-cell transcriptome analysis. Human podocytes were exposed to NLRP3 inflammasome agonists in vitro and we induced diabetes in mice with a podocyte-specific expression of the Muckle-Wells variant of NLRP3, leading to overactivation of the Nlrp3 inflammasome (Nphs2Cre;Nlrp3
A350V ) versus wildtype controls. Phenotype analysis included deep learning-based glomerular and podocyte morphometry, tissue clearing, and STED microscopy of the glomerular filtration barrier. The Nlrp3 inflammasome was blocked by feeding ß-hydroxy-butyrate., Results: Single-cell transcriptome analysis did not support relevant NLRP3 expression in parenchymal cells of the kidney. The same applied to primary human podocytes in which NLRP3 agonists did not induce IL-1β or IL-18 secretion. Diabetes induced identical glomerulomegaly in wildtype and Nphs2Cre;Nlrp3A350V mice but hyperfiltration-induced podocyte loss was attenuated and podocytes were larger in Nphs2Cre;Nlrp3A350V mice, an effect reversible with feeding the NLRP3 inflammasome antagonist ß-hydroxy-butyrate. Ultrastructural analysis of the slit diaphragm was genotype-independent hence albuminuria was identical., Conclusion: Podocytes express low amounts of the NLRP3 inflammasome, if at all, and do not produce IL-1β and IL-18, not even upon introduction of the A350V Muckle-Wells NLRP3 variant and upon induction of podocyte stress. NLRP3-mediated glomerular inflammation is limited to immune cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kunte, Marschner, Klaus, Honda, Li, Motrapu, Walz, Angelotti, Antonelli, Melica, De Chiara, Semeraro, Nelson and Anders.)- Published
- 2023
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37. Preparation of Human Kidney Progenitor Cultures and Their Differentiation into Podocytes.
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Melica ME, Angelotti ML, Antonelli G, Peired AJ, Conte C, De Chiara L, Mazzinghi B, Lazzeri E, Lasagni L, and Romagnani P
- Abstract
Kidney diseases are a global health concern. Modeling of kidney disease for translational research is often challenging because of species specificities or the postmitotic status of kidney epithelial cells that make primary cultures, for example podocytes. Here, we report a protocol for preparing primary cultures of podocytes based on the isolation and in vitro propagation of immature kidney progenitor cells subsequently differentiated into mature podocytes. This protocol can be useful for studying physiology and pathophysiology of human kidney progenitors and to obtain differentiated podocytes for modeling podocytopathies and other kidney disorders involving podocytes., Competing Interests: Competing interestsThe authors have no competing financial interests., (©Copyright : © 2023 The Authors; This is an open access article under the CC BY license.)
- Published
- 2023
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38. Chronic kidney disease in children: an update.
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Cirillo L, De Chiara L, Innocenti S, Errichiello C, Romagnani P, and Becherucci F
- Abstract
Chronic kidney disease (CKD) is a major healthcare issue worldwide. However, the prevalence of pediatric CKD has never been systematically assessed and consistent information is lacking in this population. The current definition of CKD is based on glomerular filtration rate (GFR) and the extent of albuminuria. Given the physiological age-related modification of GFR in the first years of life, the definition of CKD is challenging per se in the pediatric population, resulting in high risk of underdiagnosis in this population, treatment delays and untailored clinical management. The advent and spreading of massive-parallel sequencing technology has prompted a profound revision of the epidemiology and the causes of CKD in children, supporting the hypothesis that CKD is much more frequent than currently reported in children and adolescents. This acquired knowledge will eventually converge in the identification of the molecular pathways and cellular response to damage, with new specific therapeutic targets to control disease progression and clinical features of children with CKD. In this review, we will focus on recent innovations in the field of pediatric CKD and in particular those where advances in knowledge have become available in the last years, with the aim of providing a new perspective on CKD in children and adolescents., Competing Interests: P.R. is member of the CKJ editorial board. The other authors have no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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39. A Clinical Workflow for Cost-Saving High-Rate Diagnosis of Genetic Kidney Diseases.
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Becherucci F, Landini S, Palazzo V, Cirillo L, Raglianti V, Lugli G, Tiberi L, Dirupo E, Bellelli S, Mazzierli T, Lomi J, Ravaglia F, Sansavini G, Allinovi M, Giannese D, Somma C, Spatoliatore G, Vergani D, Artuso R, Rosati A, Cirami C, Dattolo PC, Campolo G, De Chiara L, Papi L, Vaglio A, Lazzeri E, Anders HJ, Mazzinghi B, and Romagnani P
- Subjects
- Adult, Infant, Newborn, Humans, Child, Workflow, Kidney, Genetic Testing, Urinary Tract, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic genetics
- Abstract
Significance Statement: To optimize the diagnosis of genetic kidney disorders in a cost-effective manner, we developed a workflow based on referral criteria for in-person evaluation at a tertiary center, whole-exome sequencing, reverse phenotyping, and multidisciplinary board analysis. This workflow reached a diagnostic rate of 67%, with 48% confirming and 19% modifying the suspected clinical diagnosis. We obtained a genetic diagnosis in 64% of children and 70% of adults. A modeled cost analysis demonstrated that early genetic testing saves 20% of costs per patient. Real cost analysis on a representative sample of 66 patients demonstrated an actual cost reduction of 41%. This workflow demonstrates feasibility, performance, and economic effect for the diagnosis of genetic kidney diseases in a real-world setting., Background: Whole-exome sequencing (WES) increases the diagnostic rate of genetic kidney disorders, but accessibility, interpretation of results, and costs limit use in daily practice., Methods: Univariable analysis of a historical cohort of 392 patients who underwent WES for kidney diseases showed that resistance to treatments, familial history of kidney disease, extrarenal involvement, congenital abnormalities of the kidney and urinary tract and CKD stage ≥G2, two or more cysts per kidney on ultrasound, persistent hyperechoic kidneys or nephrocalcinosis on ultrasound, and persistent metabolic abnormalities were most predictive for genetic diagnosis. We prospectively applied these criteria to select patients in a network of nephrology centers, followed by centralized genetic diagnosis by WES, reverse phenotyping, and multidisciplinary board discussion., Results: We applied this multistep workflow to 476 patients with eight clinical categories (podocytopathies, collagenopathies, CKD of unknown origin, tubulopathies, ciliopathies, congenital anomalies of the kidney and urinary tract, syndromic CKD, metabolic kidney disorders), obtaining genetic diagnosis for 319 of 476 patients (67.0%) (95% in 21 patients with disease onset during the fetal period or at birth, 64% in 298 pediatric patients, and 70% in 156 adult patients). The suspected clinical diagnosis was confirmed in 48% of the 476 patients and modified in 19%. A modeled cost analysis showed that application of this workflow saved 20% of costs per patient when performed at the beginning of the diagnostic process. Real cost analysis of 66 patients randomly selected from all categories showed actual cost reduction of 41%., Conclusions: A diagnostic workflow for genetic kidney diseases that includes WES is cost-saving, especially if implemented early, and is feasible in a real-world setting., (Copyright © 2023 by the American Society of Nephrology.)
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- 2023
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40. Intravenous Glu-plasminogen attenuates cholesterol crystal embolism-induced thrombotic angiopathy, acute kidney injury and kidney infarction.
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Lyubenov L, Shi C, Zhao D, Yang L, Lei Y, Mammadova-Bach E, de Chiara L, Semeraro R, Landini S, Romagnani P, Vörg E, Devarapu SK, Welz R, Kiessig ST, and Anders HJ
- Subjects
- Humans, Mice, Animals, Plasminogen, Mice, Inbred C57BL, Kidney, Infarction, Cholesterol, Necrosis, Acute Kidney Injury, Thrombosis, Embolism
- Abstract
Background: Cholesterol crystal (CC) embolism causes acute kidney injury (AKI) and ischaemic cortical necrosis associated with high mortality. We speculated that sustaining the fibrinolytic system with Glu-plasminogen (Glu-Plg) could be a safe way to attenuate AKI and prevent ischaemic infarction upon CC embolism., Methods: We induced CC embolism by injecting CC into the left kidney artery of C57BL/6J mice. The primary endpoint was glomerular filtration rate (GFR)., Results: Starting as early as 2 h after CC embolism, thrombotic angiopathy progressed gradually in the interlobular, arcuate and interlobar arteries. This was associated with a decrease of GFR reaching a peak at 18 h, i.e. AKI, and progressive ischaemic kidney necrosis developing between 12-48 h after CC injection. Human plasma Glu-Plg extracts injected intravenously 4 h after CC embolism attenuated thrombotic angiopathy, GFR loss as well as ischaemic necrosis in a dose-dependent manner. No bleeding complications occurred after Glu-Plg injection. Injection of an intermediate dose (0.6 mg/kg) had only a transient protective effect on microvascular occlusions lasting for a few hours without a sustained protective effect on AKI at 18-48 h or cortical necrosis, while 1.5 mg/kg were fully protective. Importantly, no bleeding complications occurred., Conclusions: These results provide the first experimental evidence that Glu-Plg could be an innovative therapeutic strategy to attenuate thrombotic angiopathy, AKI, kidney necrosis and potentially other clinical manifestations of CC embolism syndrome., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)
- Published
- 2023
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41. The Impact of the COVID-19 Pandemic on Postpartum Maternal Mental Health.
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De Chiara L, Angeletti G, Anibaldi G, Chetoni C, Gualtieri F, Forcina F, Bargagna P, Kotzalidis GD, Callovini T, Bonito M, Koukopoulos AE, and Simonetti A
- Abstract
Objectives: There are reports of mental health worsening during the COVID-19 pandemic. We aimed to assess whether this occurred in women who were pregnant at baseline (late 2019) and unaware of the pandemic, and who delivered after the implementation of COVID-19 restrictions and threat (March-April 2020). To compare the pandemic period with the pre-pandemic, we capitalized on a retrospective 2014-2015 perinatal sample which had had affective symptoms assessed., Methods: The COVID sample were administered the Postnatal Depression Scale (EPDS), Zung Self-Rating Anxiety Scale (SAS), Hypomania Checklist-32 (HCL-32), Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS) at T0 (pregnancy) and T1 (post-delivery). The Non-COVID sample had completed EPDS and HCL-32 at the same timepoints., Results: The COVID sample included 72 women, aged 21-46 years (mean = 33.25 years ± 4.69), and the Non-COVID sample included 68 perinatal women, aged 21-46 years (mean = 34.01 years ± 4.68). Our study showed greater levels of mild depression in T1 among the COVID sample compared to the Non-COVID sample. No significant differences in terms of major depression and suicidal ideation were found. The levels of hypomania were significantly different between the two groups at T1, with the COVID sample scoring higher than the Non-COVID sample. This may be related to the high levels of perceived stress we found during the postpartum evaluation in the COVID sample., Limitations: There was a relatively small sample size., Conclusions: New mothers responded to the pandemic with less mental health impairment than expected, differently from the general population. Women delivering amidst the pandemic did not differ in depressive and anxiety symptoms from their pre-pandemic scores and from pre-pandemic women. Because stress responses have high energy costs, it is optimal for maternal animals to minimize such high metabolic costs during motherhood. Evidence suggests that reproductive experience alters the female brain in adaptive ways. This maternal brain plasticity facilitates a higher purpose, the continuation of the species. This may point to the recruitment of motherhood-related resources, for potentially overcoming the effects of the pandemic on mental health.
- Published
- 2022
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42. Polyploid tubular cells and chronic kidney disease.
- Author
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De Chiara L and Romagnani P
- Subjects
- Humans, Epithelial Cells, Polyploidy, Kidney Tubules, Nephritis, Interstitial genetics, Renal Insufficiency, Chronic genetics, Nephritis
- Abstract
Defective DNA repair drives chronic kidney disease (CKD), but mechanisms are unclear. Airik and colleagues use a genetic model of defective DNA repair mimicking karyomegalic nephritis, a form of CKD characterized by tubular epithelial cells (TEC) with large nuclei and tubulointerstitial nephritis. They show that DNA damage in TEC triggers endoreplication leading to polyploid TEC and CKD. Blocking endoreplication preserved kidney function, suggesting that DNA damage triggers CKD via TEC polyploidization, questioning the concept of G2/M-arrest., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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43. Tubular cell polyploidy protects from lethal acute kidney injury but promotes consequent chronic kidney disease.
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De Chiara L, Conte C, Semeraro R, Diaz-Bulnes P, Angelotti ML, Mazzinghi B, Molli A, Antonelli G, Landini S, Melica ME, Peired AJ, Maggi L, Donati M, La Regina G, Allinovi M, Ravaglia F, Guasti D, Bani D, Cirillo L, Becherucci F, Guzzi F, Magi A, Annunziato F, Lasagni L, Anders HJ, Lazzeri E, and Romagnani P
- Subjects
- DNA metabolism, Disease Progression, Humans, Kidney metabolism, Polyploidy, RNA metabolism, Senotherapeutics, Acute Kidney Injury metabolism, Renal Insufficiency, Chronic genetics, Renal Insufficiency, Chronic metabolism
- Abstract
Acute kidney injury (AKI) is frequent, often fatal and, for lack of specific therapies, can leave survivors with chronic kidney disease (CKD). We characterize the distribution of tubular cells (TC) undergoing polyploidy along AKI by DNA content analysis and single cell RNA-sequencing. Furthermore, we study the functional roles of polyploidization using transgenic models and drug interventions. We identify YAP1-driven TC polyploidization outside the site of injury as a rapid way to sustain residual kidney function early during AKI. This survival mechanism comes at the cost of senescence of polyploid TC promoting interstitial fibrosis and CKD in AKI survivors. However, targeting TC polyploidization after the early AKI phase can prevent AKI-CKD transition without influencing AKI lethality. Senolytic treatment prevents CKD by blocking repeated TC polyploidization cycles. These results revise the current pathophysiological concept of how the kidney responds to acute injury and identify a novel druggable target to improve prognosis in AKI survivors., (© 2022. The Author(s).)
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- 2022
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44. Evaluation of Blood Soluble CD26 as a Complementary Biomarker for Colorectal Cancer Screening Programs.
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De Chiara L, Barcia-Castro L, Gallardo-Gómez M, Páez de la Cadena M, Martínez-Zorzano VS, Rodríguez-Berrocal FJ, Bujanda L, Etxart A, Castells A, Balaguer F, Jover R, Cubiella J, and Cordero OJ
- Abstract
Fecal hemoglobin immunodetection (FIT) in combination with endoscopy has been implemented to reduce mortality from colorectal cancer (CRC), although there are issues that can be improved in relation to participation rates. We studied whether the blood biomarker soluble-CD26 (sCD26), related at least in part to the immune system and inflammation, and/or its dipeptidyl peptidase enzyme activity (DPP4), could help reduce false positives. In a cohort of 1703 individuals who underwent colonoscopy and had a serum sample, sCD26 and DPP4 activity showed statistically significant differences regarding sex and age. According to the colonoscopy findings, sCD26 and DPP4 activity progressively decreased in advanced adenomas and CRC, with statistically significant differences, even between both groups; 918 of them had a FIT result ( n = 596 positive cases) with approximately 70% of these ( n = 412) false positives. With cut-offs of 440 ng/mL for sCD26, 42 mU/mL for DPP4, and 11 ng/mU for their ratio, the combined information of the three biomarkers (at least positive for one biomarker) identified almost all advanced adenomas and CRC cases in the FIT cohort with approximately half of the false positives compared to FIT. A sequential testing strategy with FIT and our blood biomarker test is proposed., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
- Published
- 2022
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- View/download PDF
45. Modelling AKI in vitro: taking organoids to the next level.
- Author
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De Chiara L and Xia Y
- Subjects
- Humans, Kidney, Kidney Tubules, Proximal, Acute Kidney Injury, Organoids
- Published
- 2022
- Full Text
- View/download PDF
46. Differentiation of crescent-forming kidney progenitor cells into podocytes attenuates severe glomerulonephritis in mice.
- Author
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Melica ME, Antonelli G, Semeraro R, Angelotti ML, Lugli G, Landini S, Ravaglia F, Regina G, Conte C, De Chiara L, Peired AJ, Mazzinghi B, Donati M, Molli A, Steiger S, Magi A, Bartalucci N, Raglianti V, Guzzi F, Maggi L, Annunziato F, Burger A, Lazzeri E, Anders HJ, Lasagni L, and Romagnani P
- Subjects
- Animals, Disease Models, Animal, Humans, Kidney metabolism, Mice, Panobinostat therapeutic use, Stem Cells metabolism, Glomerulonephritis drug therapy, Podocytes metabolism
- Abstract
Crescentic glomerulonephritis is characterized by vascular necrosis and parietal epithelial cell hyperplasia in the space surrounding the glomerulus, resulting in the formation of crescents. Little is known about the molecular mechanisms driving this process. Inducing crescentic glomerulonephritis in two Pax2Cre reporter mouse models revealed that crescents derive from clonal expansion of single immature parietal epithelial cells. Preemptive and delayed histone deacetylase inhibition with panobinostat, a drug used to treat hematopoietic stem cell disorders, attenuated crescentic glomerulonephritis with recovery of kidney function in the two mouse models. Three-dimensional confocal microscopy and stimulated emission depletion superresolution imaging of mouse glomeruli showed that, in addition to exerting an anti-inflammatory and immunosuppressive effect, panobinostat induced differentiation of an immature hyperplastic parietal epithelial cell subset into podocytes, thereby restoring the glomerular filtration barrier. Single-cell RNA sequencing of human renal progenitor cells in vitro identified an immature stratifin-positive cell subset and revealed that expansion of this stratifin-expressing progenitor cell subset was associated with a poor outcome in human crescentic glomerulonephritis. Treatment of human parietal epithelial cells in vitro with panobinostat attenuated stratifin expression in renal progenitor cells, reduced their proliferation, and promoted their differentiation into podocytes. These results offer mechanistic insights into the formation of glomerular crescents and demonstrate that selective targeting of renal progenitor cells can attenuate crescent formation and the deterioration of kidney function in crescentic glomerulonephritis in mice.
- Published
- 2022
- Full Text
- View/download PDF
47. Erratum to: FC041 tubular epithelial cell polyploidy is essential to survive AKI but contributes to CKD progression.
- Author
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De Chiara L, Lazzeri E, and Romagnani P
- Published
- 2022
- Full Text
- View/download PDF
48. Erratum to: MO065 tubular epithelial cell polyploidization is required to survive AKI but promotes CKD development.
- Author
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De Chiara L, Lazzeri E, Angelotti ML, Conte C, Peired AJ, Antonelli G, Melica ME, Mazzinghi B, Lasagni L, and Romagnani P
- Published
- 2022
- Full Text
- View/download PDF
49. Molecular Mechanisms and Biomarkers Associated with Chemotherapy-Induced AKI.
- Author
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De Chiara L, Lugli G, Villa G, Raglianti V, Husain-Syed F, Ravaglia F, Romagnani P, and Lazzeri E
- Subjects
- Acute Disease, Biomarkers, Humans, Acute Kidney Injury chemically induced, Acute Kidney Injury complications, Acute Kidney Injury diagnosis, Antineoplastic Agents adverse effects, Renal Insufficiency, Chronic complications
- Abstract
Acute kidney injury (AKI) is a life-threatening condition characterized by a rapid and transient decrease in kidney function. AKI is part of an array of conditions collectively defined as acute kidney diseases (AKD). In AKD, persistent kidney damage and dysfunction lead to chronic kidney disease (CKD) over time. A variety of insults can trigger AKI; however, chemotherapy-associated nephrotoxicity is increasingly recognized as a significant side effect of chemotherapy. New biomarkers are urgently needed to identify patients at high risk of developing chemotherapy-associated nephrotoxicity and subsequent AKI. However, a lack of understanding of cellular mechanisms that trigger chemotherapy-related nephrotoxicity has hindered the identification of effective biomarkers to date. In this review, we aim to (1) describe the known and potential mechanisms related to chemotherapy-induced AKI; (2) summarize the available biomarkers for early AKI detection, and (3) raise awareness of chemotherapy-induced AKI.
- Published
- 2022
- Full Text
- View/download PDF
50. The Pathology Lesion Patterns of Podocytopathies: How and why?
- Author
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Ravaglia F, Melica ME, Angelotti ML, De Chiara L, Romagnani P, and Lasagni L
- Abstract
Podocytopathies are a group of proteinuric glomerular disorders driven by primary podocyte injury that are associated with a set of lesion patterns observed on kidney biopsy, i.e., minimal changes, focal segmental glomerulosclerosis, diffuse mesangial sclerosis and collapsing glomerulopathy. These unspecific lesion patterns have long been considered as independent disease entities. By contrast, recent evidence from genetics and experimental studies demonstrated that they represent signs of repeated injury and repair attempts. These ongoing processes depend on the type, length, and severity of podocyte injury, as well as on the ability of parietal epithelial cells to drive repair. In this review, we discuss the main pathology patterns of podocytopathies with a focus on the cellular and molecular response of podocytes and parietal epithelial cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ravaglia, Melica, Angelotti, De Chiara, Romagnani and Lasagni.)
- Published
- 2022
- Full Text
- View/download PDF
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