Synthesis and Anti-Diabetic Activity of an 8-Purine Derivative as a Novel DPP-4 Inhibitor in Obese Diabetic Zücker Rats

Meriem Chayah,1– 3 Angélica Luque-González,1 Verónica Gómez-Pérez,1 Diego Salagre,4,5 Amjad Al-Shdaifat,6 Joaquín María Campos,1,2 Ana Conejo-García,1,2 Ahmad Agil2,4,5 1Department of Medicinal and Organic Chemistry and Excellence Research Unit of Chemistry Applied to Biomedicine and the Environment, Faculty of Pharmacy, University of Granada, Granada, Spain; 2Biosanitary Institute of Granada (Ibs.granada), SAS-University of Granada, Granada, Spain; 3Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government (GENYO), Granada, Spain; 4Department of Pharmacology, Faculty of Medicine, University of Granada, Granada, Spain; 5Federico Oloriz Neuroscience Institute, University of Granada, Granada, Spain; 6Department of Medicine and Family Medicine, Faculty of Medicine, Hashemite University, Zarqa, JordaniaCorrespondence: Ahmad Agil; Ana Conejo-García, Email [email protected]; [email protected]: Type 2 diabetes mellitus (T2DM) is one of the world’s principal metabolic diseases characterized by chronic hyperglycemia. The gut incretin hormones, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), which has been proposed as a new treatment for T2DM, are extensively metabolized by Dipeptidyl peptidase 4 (DPP-4). Inhibitors of DPP-4 block the degradation of GLP-1 and GIP and may increase their natural circulating levels, favoring glycemic control in T2DM. A novel and potent selective inhibitor of DPP-4 with an 8-purine derived structure ( 1) has been developed and tested in vitro and in vivo in Zücker obese diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome and T2DM to assess the inhibitory activity using vildagliptin as reference standard. ZDF rats were subdivided into three groups (n = 7/group), control (C-ZDF), and those treated with compound 1 (Compound 1-ZDF) and with vildagliptin (V-ZDF), both at 10 mg/kg/d rat body weight, in their drinking water for 12 weeks, and a group of lean littermates (ZL) was used. ZDF rats developed DM (fasting hyperglycemia, 425 ± 14.8 mg/dL; chronic hyperglycemia, HbA1c 8.5 ± 0.4%), compared to ZL rats. Compound 1 and vildagliptin reduced sustained HbAl1c (14% and 10.6%, P < 0.05, respectively) and fasting hyperglycemia values (24% and 19%, P < 0.05, respectively) compared to C-ZDF group (P < 0.001). Compound 1 and vildagliptin have shown a potent activity with an IC50 value of 4.92 and 3.21 μM, respectively. These data demonstrate that oral compound 1 administration improves diabetes in ZDF rats by the inhibitory effect on DPP-4, and the potential to be a novel, efficient and tolerable approach for treating diabetes of obesity-related T2DM, in ZDF rats.Keywords: diabetes mellitus type 2, DPP-4 inhibitors, purine derivatives, ZDF rat

Engineering a Spin-Orbit Bandgap in Graphene-Tellurium Heterostructures

Intensive research has focused on harnessing the potential of graphene for electronic, optoelectronic, and spintronic devices by generating a bandgap at the Dirac point and enhancing the spin-orbit interaction in the graphene layer. Proximity to heavy p elements is a promising approach; however, their interaction in graphene heterostructures has not been as intensively studied as that of ferromagnetic, noble, or heavy d metals, neither as interlayers nor as substrates. In this study, the effective intercalation of Te atoms in a graphene on Ir(111) heterostructure is achieved. Combining techniques such as low energy electron diffraction and scanning tunneling microscopy, the structural evolution of the system as a function of the Te coverage is elucidated, uncovering up to two distinct phases. The presented angle-resolved photoemission spectroscopy analysis reveals the emergence of a bandgap of about 240 meV in the Dirac cone at room temperature, which preserves its characteristic linear dispersion. Furthermore, a pronounced n-doping effect induced by Te in the heterostructure is also observed, and remarkably the possibility of tuning the Dirac point energy towards the Fermi level by reducing the Te coverage while maintaining the open bandgap is demonstrated. Spin-resolved measurements unveil a non-planar chiral spin texture with significant splitting values for both in-plane and out-of-plane spin components. These experimental findings are consistent with the development of a quantum spin Hall phase, where a Te-enhanced intrinsic spin orbit coupling in graphene surpasses the Rashba one and promotes the opening of the spin-orbit bandgap.Comment: 9 pages, 4 figure

Photoluminescence and cathodoluminescence of Eu:La2O3 nanoparticles synthesized by several methods

Abstract : Europium-doped La2O3 nanocrystalline powders with sizes ranging from 4 nm to 300 nm have been obtained by the modified Pechini, hydrothermal with conventional furnace, hydrothermal with microwave furnace, and precipitation with ultrasonic bath methods. X-ray diffraction techniques were used to study the evolution of the prepared gels towards the desired crystalline phase. We determined the size and the morphology of the nanoparticles by electronic microscopy. Finally, we studied and analyzed the luminescence properties of the trivalent europium in the hexagonal La2O3 nanocrystals by photoluminescence and cathodoluminescence

Optimizing both catalyst preparation and catalytic behaviour for the oxidative dehydrogenation of ethane of Ni-Sn-O catalysts

[EN] Bulk Ni-Sn-O catalysts have been synthesized, tested in the oxidative dehydrogenation of ethane and characterized by several physicochemical techniques. The catalysts have been prepared by evaporation of the corresponding salts using several additives in the synthesis gel, i.e. ammonium hydroxide, nitric acid, glyoxylic acid or oxalic acid, in the synthesis gel. The catalysts were finally calcined at 500 degrees C in air. Important changes in the catalytic behaviour have been observed depending on the additive. In fact, an important improvement in the catalytic performance is observed especially when some additives, such as glyoxylic or oxalic acid, are used. Thus the productivity to ethylene multiplies by 6 compared to the reference Ni-Sn-O catalyst if appropriate templates are used, and this is the result of an improvement in both the catalytic activity and the selectivity to ethylene. This improved performance has been explained in terms of the decrease of the crystallite size (and the increase in the surface area of catalyst) as well as the modification of the lattice parameter of nickel oxide.The authors would like to acknowledge the DGICYT in Spain (CTQ2015-68951-C3-1-R and CTQ2012-37925-C03-2) for financial support. We also thank the University of Valencia and SCSIE-UV for assistanceSolsona Espriu, BE.; López Nieto, JM.; Agouram, S.; Soriano Rodríguez, MD.; Dejoz, A.; Vázquez, MI.; Concepción Heydorn, P. (2016). Optimizing both catalyst preparation and catalytic behaviour for the oxidative dehydrogenation of ethane of Ni-Sn-O catalysts. Topics in Catalysis. 59(17-18):1564-1572. https://doi.org/10.1007/s11244-016-0674-zS156415725917-18Heracleous E, Lee AF, Wilson K, Lemonidou AA (2005) J Catal 231:159–171Heracleous E, Lemonidou AA (2006) J Catal 237:162–174Savova B, Loridant S, Filkova D, Millet JMM (2010) Appl Catal A 390:148–157Heracleous E, Lemonidou AA (2010) J Catal 270:67–75Solsona B, Nieto JML, Concepcion P, Dejoz A, Ivars F, Vazquez MI (2011) J Catal 280:28–39Skoufa Z, Heracleous E, Lemonidou AA (2012) Catal Today 192:169–176Zhu H, Ould-Chikh S, Anjum DH, Sun M, Biausque G, Basset JM, Caps V (2012) J Catal 285:292–303Skoufa Z, Heracleous E, Lemonidou AA (2012) Chem Eng Sci 84:48–56Zhu H, Rosenfeld DC, Anjum DH, Caps V, Basset JM (2015) ChemSusChem 8:1254–1263Heracleous E, Lemonidou AA (2015) J Catal 322:118–129Solsona B, Concepcion P, Demicol B, Hernandez S, Delgado JJ, Calvino JJ, Nieto JML (2012) J Catal 295:104–114Nieto JML, Solsona B, Grasselli RK, Concepción P (2014) Top Catal 57:1248–1255Popescu I, Skoufa Z, Heracleous E, Lemonidou AA, Marcu IC (2015) PCCP 17:8138–8147Zhang X, Gong Y, Yu G, Xie Y (2002) J Mol Catal A 180:293–298Popescu I, Skoufa Z, Heracleous E, Lemonidou A, Marcu I-C (2015) Phys Chem Chem Phys 17:8138–8147Nakamura KI, Miyake T, Konishi T, Suzuki T (2006) J Mol Catal A 260:144–151Solsona B, Dejoz AM, Vazquez MI, Ivars F, Nieto JML (2009) Top Catal 52:751–757Bortolozzi JP, Gutierrez LB, Ulla MA (2013) Appl Catal A 452:179–188Takeguchi T, Furukawa S, Inoue M (2001) J Catal 202:14–24Richardson JT, Turk B, Twigg MV (1996) Appl Catal 148:97–112Biju V, Khadar MA (2002) J Nanopart Res 4:247–253Van Veenendaal MA, Sawatzky GA (1993) Phys Rev Lett 70:2459–2462Vedrine JC, Hollinger G, Duc TM (1978) J Phys Chem 82:1515–1520Salagre P, Fierro JLG, Medina F, Sueiras JE (1996) J Mol Catal A 106:125–13

Corrigendum to “Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats” [Biomed. Pharmacother. 172 (2024) 116314]

The authors regret the human error made in funding. Following the instructions of the Spanish Ministry to have no problem with the payment, the funding given had data from funders repeated, and following their instructions, the funding should simply appear in the manuscript as follows: Funding: This study was supported by grant PID2021-125900OB-I00 funded by MCIN/AEI/10.13039/501100011033 and, ERDF “A way of making Europe”. The authors would like to apologise for any inconvenience caused.This study was supported by grant PID2021-125900OB-I00 funded by MCIN/AEI/10.13039/501100011033 and, ERDF “A way of making Europe”

Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats

Melatonin acute treatment limits obesity of young Zücker diabetic fatty (ZDF) rats by non-shivering thermogenesis (NST). We recently showed melatonin chronically increases the oxidative status of vastus lateralis (VL) in both obese and lean adult male animals. The identification of VL skeletal muscle-based NST by uncoupling of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA)- sarcolipin (SLN) prompted us to investigate whether melatonin is a SERCA-SLN calcium futile cycle uncoupling and mitochondrial biogenesis enhancer. Obese ZDF rats and lean littermates (ZL) of both sexes were subdivided into two subgroups: control (C) and 12 weeks orally melatonin treated (M) (10 mg/kg/day). Compared to the control groups, melatonin decreased the body weight gain and visceral fat in ZDF rats of both sexes. Melatonin treatment in both sex obese rats restored the VL muscle skin temperature and sensitized the thermogenic effect of acute cold exposure. Moreover, melatonin not only raised SLN protein levels in the VL of obese and lean rats of both sexes; also, the SERCA activity. Melatonin treatment increased the SERCA2 expression in obese and lean rats (both sexes), with no effects on SERCA1 expression. Melatonin increased the expression of thermogenic genes and proteins (PGC1-α, PPARγ, and NRF1). Furthermore, melatonin treatment enhanced the expression ratio of P-CaMKII/CaMKII and P-AMPK/AMPK. In addition, it rose mitochondrial biogenesis. These results provided the initial evidence that chronic oral melatonin treatment triggers the CaMKII/AMPK/PGC1α axis by upregulating SERCA2-SLN-mediated NST in ZDF diabetic rats of both sexes. This may further contribute to the body weight control and metabolic benefits of melatonin

The use of electroconvulsive therapy (ECT) en bloc in Denmark: a nationwide register-based study

Electroconvulsive therapy (ECT) en bloc is defined as ECT administered on 2–3 consecutive days. In Denmark, ECT en bloc is recommended for severe conditions such as catatonia, treatment-resistant mania/psychosis, or imminent risk of suicide. To our knowledge, there are no recent reports on the use of ECT en bloc in clinical practice. Here, we provide such a report. We characterized the use of ECT en bloc in the period from 2006-2019 based on data from Danish national registers. Furthermore, we compared mortality rates between patients receiving ECT en bloc and patients receiving standard regimen ECT (not en bloc). We identified 2173 patients who received a total of 2734 ECT en bloc treatment courses in Denmark in the period from 2006 to 2019 (6% of the total number of ECT treatment courses). The use of ECT en bloc was stable over the study period (range: 138–196 patients per year). The most common treatment indications were unipolar depression (41%), psychotic disorder (23%), and bipolar disorder (20%). The vast majority (90%) received ECT en bloc voluntarily. The 1-year mortality rate ratio for ECT en bloc compared to standard regimen ECT was 1.42 (95%CI: 1.03–1.95). The use of ECT en bloc in Denmark is stable both in terms of the number of patients treated and treatment indications. In keeping with ECT en bloc being used for severe conditions, those receiving this treatment have a higher mortality rate compared to those receiving standard ECT, warranting careful monitoring during follow-up.</p

Characterization and catalytic properties of several KMg1−xPdxF3 with perovskite-like structures for the hydroconversion of CHClF2

International audienceSeveral KMg1−xPdxF3 samples were prepared in aqueous medium at mild conditions (333 K) and characterized by different techniques. The enlargement of their cell parameters has been associated with the insertion of Pd into the structure. After reduction, these compounds were tested in the hydrodechlorination reaction of CHClF2. Reduced KMg1−xPdxF3 samples showed higher selectivity to the desirable product CH2F2 (80-90%) than one Pd/KMgF3 catalyst where the main product was CH3F. The upward shift of the CO adsorption bands observed from the IR spectra for the reduced palladium perovskite indicates the lower electron density of Pd obtained from the reduction of KMg1−xPdxF3 samples. This modifies the mechanism of the reaction allowing the removal of one chlorine atom and therefore, favoring the formation of CH2F2

Risk Calculators in Bipolar Disorder: A Systematic Review

Introduction: Early recognition of bipolar disorder improves the prognosis and decreases the burden of the disease. However, there is a significant delay in diagnosis. Multiple risk factors for bipolar disorder have been identified and a population at high-risk for the disorder has been more precisely defined. These advances have allowed the development of risk calculators to predict individual risk of conversion to bipolar disorder. This review aims to identify the risk calculators for bipolar disorder and assess their clinical applicability. Methods: A systematic review of original studies on the development of risk calculators in bipolar disorder was performed. The studies' quality was evaluated with the Newcastle-Ottawa Quality Assessment Form for Cohort Studies and according to recommendations of the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis Initiative. Results: Three studies met the inclusion criteria; one developed a risk calculator of conversion from major depressive episode to bipolar disorder; one of conversion to new-onset bipolar spectrum disorders in offspring of parents with bipolar disorder; and the last one of conversion in youths with bipolar disorder not-otherwise-specified. Conclusions: The calculators reviewed in this article present good discrimination power for bipolar disorder, although future replication and validation of the models is needed.info:eu-repo/semantics/publishedVersio