5 research outputs found
Synthetic conjugates of ursodeoxycholic acid inhibit cystogenesis in experimental models of polycystic liver disease
Background and aims: polycystic 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 results: here, 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. Conclusions: these UDCA-HDAC6i conjugates open a therapeutic avenue for PLDs
Quince (Cydonia oblonga) in vitro plant root formation through an automated temporary inmersion system, and its acclimation
ArtĂculo cientĂficoQuince (Cydonia oblonga) is a non-traditional fruit tree found in Costa Rica that has
therapeutic and nutritional properties; however its slow growth and root formation prevents the production
of a homogeneous population when using conventional farming techniques. Hence, the aim of this research
project was to generate uniform plant material in a reduced time span using a temporary immersion bioreactor
system (RITAS Âź). A semisolid rooting MS culture medium supplemented with 0.1 mg L-1 NAA; 0.3 mg L-1
IBA and 3% sucrose (pH 6.5), developed in the Centro de InvestigaciĂłn en BiotecnologĂa (CIB), Instituto
TecnolĂłgico de Costa Rica (ITCR), in Cartago, was used as a reference medium. Four different variations
in the sucrose concentration (1%, 2%, 3%, and 4%) were performed in liquid medium. Each trial was
evaluated with in vitro plants which had been previously exposed to the culture medium of the corresponding
treatments, in a stationary mode and for a 15 day long period, and with in vitro plants without any previous
treatment (a total of eight treatments). The comparison of the root formation percentages evidenced the clear
effect of sucrose concentration used, with the best results obtained when using the 2% sucrose trial with no
pre-treatment (73.3%). The in vitro plants were acclimated in cylinders made out of peat, have previously
been disinfected with fungicide, and placed in a humidity chamber at a 20.5°C average temperature and a
75,5% relative humidity for the establishment of weekly fertilizing cycles. The acclimation process generated
an 80% survival rate, since several seedlings experienced stem strangulation caused by a fungal attack.
The conidiophores identified through optical and scanning electron microscopy evidenced the presence of
Cladosporium spp., which was controlled with carbendazim and iprodione fungicides