Evidence map›Paper›PMID 32145077›Full record

ArticleHepatology (Baltimore, Md.)2021

Synthetic Conjugates of Ursodeoxycholic Acid Inhibit Cystogenesis in Experimental Models of Polycystic Liver Disease.

Francisco J Caballero-Camino, Ivan Rivilla, Elisa Herraez, Oscar Briz, Alvaro Santos-Laso, Laura Izquierdo-Sanchez, Pui Y Lee-Law, Pedro M Rodrigues, Patricia Munoz-Garrido, Sujeong Jin and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 2 countries.

Francisco J Caballero-CaminoDepartment of Organic Chemistry I, Center of Innovation in Advanced Chemistry (ORFEO-CINQA), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Donostia International Physics Center (DIPC), Donostia-San Sebastian, Spain.
Ivan RivillaDepartment of Organic Chemistry I, Center of Innovation in Advanced Chemistry (ORFEO-CINQA), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Donostia International Physics Center (DIPC), Donostia-San Sebastian, Spain.ORCID 0000-0003-1984-7183
Elisa HerraezExperimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.ORCID 0000-0001-9271-3320
Oscar BrizExperimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.ORCID 0000-0001-6891-1554
Alvaro Santos-LasoDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, UPV/EHU, Donostia-San Sebastian, Spain.ORCID 0000-0001-9810-4913
Laura Izquierdo-SanchezDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, UPV/EHU, Donostia-San Sebastian, Spain.
Pui Y Lee-LawDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, UPV/EHU, Donostia-San Sebastian, Spain.
Pedro M RodriguesDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, UPV/EHU, Donostia-San Sebastian, Spain.ORCID 0000-0001-6193-7436
Patricia Munoz-GarridoDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, UPV/EHU, Donostia-San Sebastian, Spain.
Sujeong JinThe Hormel Institute, University of Minnesota, Austin, MN.
Estanislao PeixotoThe Hormel Institute, University of Minnesota, Austin, MN.ORCID 0000-0001-5226-9747
Seth RichardThe Hormel Institute, University of Minnesota, Austin, MN.
Sergio A GradiloneThe Hormel Institute, University of Minnesota, Austin, MN.
Maria J PerugorriaDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, UPV/EHU, Donostia-San Sebastian, Spain.ORCID 0000-0002-7636-0972
Manel EstellerJosep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain.ORCID 0000-0003-4490-6093
Luis BujandaDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, UPV/EHU, Donostia-San Sebastian, Spain.ORCID 0000-0002-4353-9968
Jose J G MarinExperimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.ORCID 0000-0003-1186-6849
Jesus M BanalesDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, UPV/EHU, Donostia-San Sebastian, Spain.ORCID 0000-0002-5224-2373
Fernando P CossíoDepartment of Organic Chemistry I, Center of Innovation in Advanced Chemistry (ORFEO-CINQA), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Donostia International Physics Center (DIPC), Donostia-San Sebastian, Spain.ORCID 0000-0002-4526-2122
Biogipuzkoa Health Research Institute · ESUniversity of Minnesota · USInstituto de Salud Carlos III · ESUniversidad de Salamanca · ESUniversity of the Basque Country · ESIkerbasque · ESInstitució Catalana de Recerca i Estudis Avançats · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsPolycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of symptomatic biliary cysts. Current surgical and pharmacological approaches are ineffective, and liver transplantation represents the only curative option. Ursodeoxycholic acid (UDCA) and histone deacetylase 6 inhibitors (HDAC6is) have arisen as promising therapeutic strategies, but with partial benefits. APPROACH AND

resultsHere, we tested an approach based on the design, synthesis, and validation of a family of UDCA synthetic conjugates with selective HDAC6i capacity (UDCA-HDAC6i). Four UDCA-HDAC6i conjugates presented selective HDAC6i activity, UDCA-HDAC6i #1 being the most promising candidate. UDCA orientation within the UDCA-HDAC6i structure was determinant for HDAC6i activity and selectivity. Treatment of polycystic rats with UDCA-HDAC6i #1 reduced their hepatomegaly and cystogenesis, increased UDCA concentration, and inhibited HDAC6 activity in liver. In cystic cholangiocytes UDCA-HDAC6i #1 restored primary cilium length and exhibited potent antiproliferative activity. UDCA-HDAC6i #1 was actively transported into cells through BA and organic cation transporters.

conclusionsThese UDCA-HDAC6i conjugates open a therapeutic avenue for PLDs.

Indexed as

ApoptosisAnimalsBile Acids and SaltsBile DuctsCell ProliferationCystsDisease Models, AnimalHistone Deacetylase 6LiverLiver DiseasesRandom AllocationRatsSynthetic DrugsUrsodeoxycholic AcidBile Acids and SaltsHistone Deacetylase 6Synthetic DrugsUrsodeoxycholic Acid

Identifiers

PMID32145077
PMCPMC7891670
OpenAlexW3009063411

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.