Non-specific inhibition of dipeptidyl peptidases 8/9 by dipeptidyl peptidase 4 inhibitors negatively affects mesenchymal stem cell differentiation

DPP4 may play a relevant role in MSC differentiation into osteoblasts or adipocytes. Dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4i), such as sitagliptin and vildagliptin, are used as antidiabetic drugs. However, vildagliptin is not a specific DPP4i and also inhibits DPP8/9, which is involved in energy metabolism and immune regulation. The aim of this study is to evaluate how sitagliptin, vildagliptin or 1G244 (a DPP8/9 specific inhibitor) may influence cell viability, as well as osteogenic and adipogenic differentiation in human mesenchymal stem cells (MSC). Viability, apoptosis, osteoblastogenesis and adipogenesis markers, as well as protein synthesis of β-catenin, were studied in MSC cultures induced to differentiate into osteoblasts or adipocytes in the presence or absence of sitagliptin, vildagliptin or 1G244. The two tested DPP4i did not affect MSC viability, but 1G244 significantly decreased it in MSC and osteoblast-induced cells. Additionally, 1G244 and vildagliptin inhibited osteogenesis and adipogenesis, unlike sitagliptin. Therefore, inhibition of DPP4 did not affect MSC viability and differentiation, whereas inhibition of DPP8/9 negatively affected MSC. To the best of our knowledge, these results show for the first time that DPP8/9 have an important role in the viability and differentiation of human MSC. This data can be considered for human clinical use of drugs affecting DPP8/9 activity

Ischemia/reperfusion increases the oxidized state of specific cys residues in proteins from mitochondrial supopulation from rat miocardium that are protected by ischemia preconditioning

Comunicaciones a congreso

Short communication. In vitro oocyte maturation and fertilization rates in the Spanish Lidia bovine breed

The Lidia bovine breed is the most successful cattle breed on the Iberian Peninsula, also considered a hallmark of Spanish tradition and image around the world. The aims of the study were to characterize the oocyte recovery rates and to evaluate the effect of two standard in vitro maturation protocols on oocyte maturation (cumulus expansion and nuclear maturation) and fertilization rates after in vitro fertilization in this breed. For this purpose, 261 ovaries from Lidia cows were processed obtaining 1,125 viable cumulus oocyte complexes (COCs). The oocyte recovery rate obtained (4.31 viable COCs per ovary) was lower than those described previously in other studied breeds. Maturation rates were evaluated in two different oocyte maturation media with (M1) and without (M2) hormonal supplementation. The percentage of COCs with expanded cumulus cells was significantly lower in M1 (74.35%) compared with M2 (82.25%). Metaphase II (MII) rates (67.75% in M1 and 73.18% in M2) were similar to previous studies in different cattle populations. M2 significantly improved the percentage of COCs with their cumulus cells expanded (p < 0.01) and nuclear maturation rates (p < 0.05), but it did not affect the fertilization percentages obtained in this experiment. In conclusion, our study suggests that oocytes of the Lidia cattle breed can be obtained, matured and fertilized following standard protocols previously used in other cattle breeds

Multivariate optimization of the KharascheSosnovsky allylic oxidation of olefins

The multivariate optimization method known as simplex is applied to the KharascheSosnovsky allylic oxidation of double bonds. By applying this method, the amounts of three variables (copper source, oxidant, and additive) are optimized at the same time. Under the conditions thus obtained the reaction takes place in a considerable shorter time, being the alkene the limiting reagent. These conditions are applied to some monoterpenes and sesquiterpenes leading regioselectively to the corresponding benzoate esters, opening a route to the employment of this reaction in the synthesis of more complex molecules

Flavonoid Phloretin Inhibits Adipogenesis and Increases OPG Expression in Adipocytes Derived from Human Bone-Marrow Mesenchymal Stromal-Cells

Phloretin (a flavonoid abundant in apple), has antioxidant, anti-inflammatory, and glucose-transporter inhibitory properties. Thus, it has interesting pharmacological and nutraceutical potential. Bone-marrow mesenchymal stem cells (MSC) have high differentiation capacity, being essential for maintaining homeostasis and regenerative capacity in the organism. Yet, they preferentially differentiate into adipocytes instead of osteoblasts with aging. This has a negative impact on bone turnover, remodeling, and formation. We have evaluated the effects of phloretin on human adipogenesis, analyzing MSC induced to differentiate into adipocytes. Expression of adipogenic genes, as well as genes encoding OPG and RANKL (involved in osteoclastogenesis), protein synthesis, lipid-droplets formation, and apoptosis, were studied. Results showed that 10 and 20 µM phloretin inhibited adipogenesis. This effect was mediated by increasing beta-catenin, as well as increasing apoptosis in adipocytes, at late stages of differentiation. In addition, this chemical increased OPG gene expression and OPG/RANKL ratio in adipocytes. These results suggest that this flavonoid (including phloretin-rich foods) has interesting potential for clinical and regenerative-medicine applications. Thus, such chemicals could be used to counteract obesity and prevent bone-marrow adiposity. That is particularly useful to protect bone mass and treat diseases like osteoporosis, which is an epidemic worldwide

First case of sterility associated with sex chromosomal abnormalities in a jenny

Chromosomal abnormalities are one of the main causes of genetic infertility in horses. Currently, their detection rate is rising due to the use of new diagnostic tools employing molecular markers linked to the sex chromosome pair. Despite genetic similarities, there are no previous reports of sterility associated with chromosomal abnormalities in the domestic donkey (Equus asinus). Hereby, we determined the presence of a chromosomal mosaicism in a female donkey with reproductive problems using molecular methodologies developed for horses. A two-and- a- half- year- old jenny characterized by morphological abnormalities of the reproductive tract was cytogenetically analysed using conventional and fluorescent techniques and a group of microsatellite markers (short tandem repeat, STR). At the same time, five ultrasound measures of the reproductive tract were taken and compared with eight contemporary jennies of the same breed. After slaughter, morphological examinations showed that the case study had a blind vaginal vestibule defining an empty pouch that covered the entrance of the cervical os. Histopathological studies demonstrated that this abnormal structure was compatible with a remnant hymen. Molecular markers, STR and fluorescent in situ hybridization determinations revealed that the animal was a 62, XX/61,X mosaic and, therefore, the first case of chromosomal abnormalities in the sex pair reported in donkeys.Instituto de Genética Veterinari

Ischemic preconditioning and ischaemia-reperfusion: key role of connexin43 and mitochondrial complexes

Comunicaciones a congreso

Copper-iron mixed oxide supported onto cordierite honeycomb as a heterogeneous catalyst in the Kharasch-Sosnovsky oxidation of cyclohexene

A copper-iron mixed oxide was deposited by the washcoating procedure over cordierite honeycomb monoliths for its use as a heterogeneous catalyst in organic synthesis processes. In particular, the prepared catalyst, characterized by techniques such as X-ray fluorescence, X-ray diffraction, SEM-EDS, laser granulometry, adherence tests, Temperature-Programmed Oxidation and Temperature-Programmed Reduction, showed an excellent yield and stability in the selective production of the allylic ester derived from the Kharasch-Sosnovsky oxidation of cyclohexene with benzoic acid. The use of a structured catalyst here proposed opens up an interesting alternative to homogeneous catalysis in the field of synthetic chemistry. © 2021 The AuthorsThe authors thank the Ministry of Economy and Competitiveness of Spain (Projects MAT2017-85-719-R , and AGL2017-88083-R ), the Junta de Andalucía ( FQM-110 and FQM-169 groups), and the Institute of Electron Microscopy and Materials (IMEYMAT) of Cadiz University (UCA) (Projects HOMOGREEN and NUPRECAT) for their financial support. They also acknowledge the SC-ICYT of the UCA for using its XRD NMR, and electron microscopy division facilities

Dynamically weighted evolutionary ordinal neural network for solving an imbalanced liver transplantation problem

Objective Create an efficient decision-support model to assist medical experts in the process of organ allocation in liver transplantation. The mathematical model proposed here uses different sources of information to predict the probability of organ survival at different thresholds for each donor–recipient pair considered. Currently, this decision is mainly based on the Model for End-stage Liver Disease, which depends only on the severity of the recipient and obviates donor–recipient compatibility. We therefore propose to use information concerning the donor, the recipient and the surgery, with the objective of allocating the organ correctly. Methods and materials The database consists of information concerning transplants conducted in 7 different Spanish hospitals and the King's College Hospital (United Kingdom). The state of the patients is followed up for 12 months. We propose to treat the problem as an ordinal classification one, where we predict the organ survival at different thresholds: less than 15 days, between 15 and 90 days, between 90 and 365 days and more than 365 days. This discretization is intended to produce finer-grain survival information (compared with the common binary approach). However, it results in a highly imbalanced dataset in which more than 85% of cases belong to the last class. To solve this, we combine two approaches, a cost-sensitive evolutionary ordinal artificial neural network (ANN) (in which we propose to incorporate dynamic weights to make more emphasis on the worst classified classes) and an ordinal over-sampling technique (which adds virtual patterns to the minority classes and thus alleviates the imbalanced nature of the dataset). Results The results obtained by our proposal are promising and satisfactory, considering the overall accuracy, the ordering of the classes and the sensitivity of minority classes. In this sense, both the dynamic costs and the over-sampling technique improve the base results of the considered ANN-based method. Comparing our model with other state-of-the-art techniques in ordinal classification, competitive results can also be appreciated. The results achieved with this proposal improve the ones obtained by other state-of-the-art models: we were able to correctly predict more than 73% of the transplantation results, with a geometric mean of the sensitivities of 31.46%, which is much higher than the one obtained by other models. Conclusions The combination of the proposed cost-sensitive evolutionary algorithm together with the application of an over-sampling technique improves the predictive capability of our model in a significant way (especially for minority classes), which can help the surgeons make more informed decisions about the most appropriate recipient for an specific donor organ, in order to maximize the probability of survival after the transplantation and therefore the fairness principle