Spectroscopic Characterization and Biological Activity of Hesperetin Schiff Bases and Their Cu(II) Complexes

The three Schiff base ligands, derivatives of hesperetin, HHSB (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]isonicotinohydrazide), HIN (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]benzhydrazide) and HTSC (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]thiosemicarbazide) and their copper complexes, CuHHSB, CuHIN, and CuHTSC were designed, synthesized and analyzed in terms of their spectral characterization and the genotoxic activity. Their structures were established using several methods: elemental analysis, FT-IR, UV-Vis, EPR, and ESI-MS. Spectral data showed that in the acetate complexes the tested Schiff bases act as neutral tridentate ligand coordinating to the copper ion through two oxygen (or oxygen and sulphur) donor atoms and a nitrogen donor atom. EPR measurements indicate that in solution the complexes keep their structures with the ligands remaining bound to copper(II) in a tridentate fashion with (O^–, N, O_ket) or (O^–, N, S) donor set. The genotoxic activity of the compounds was tested against model tumour (HeLa and Caco-2) and normal (LLC-PK1) cell lines. In HeLa cells the genotoxicity for all tested compounds was noticed, for HHSB and CuHHSB was the highest, for HTSC and CuHTSC–the lowest. Generally, Cu complexes displayed lower genotoxicity to HeLa cells than ligands. In the case of Caco-2 cell line HHSB and HTSC induced the strongest breaks to DNA. On the other side, CuHHSB and CuHTSC induced the highest DNA damage against LLC-PK1.     

Relative Contribution of Blood Pressure and Renal Sympathetic Nerve Activity to Proximal Tubular Sodium Reabsorption via NHE3 Activity

We examined the effects of an acute increase in blood pressure (BP) and renal sympathetic nerve activity (rSNA) induced by bicuculline (Bic) injection in the paraventricular nucleus of hypothalamus (PVN) or the effects of a selective increase in rSNA induced by renal nerve stimulation (RNS) on the renal excretion of sodium and water and its effect on sodium-hydrogen exchanger 3 (NHE3) activity. Uninephrectomized anesthetized male Wistar rats were divided into three groups: (1) Sham; (2) Bic PVN: (3) RNS + Bic injection into the PVN. BP and rSNA were recorded, and urine was collected prior and after the interventions in all groups. RNS decreased sodium (58%) and water excretion (53%) independently of BP changes (p < 0.05). However, after Bic injection in the PVN during RNS stimulation, the BP and rSNA increased by 30% and 60% (p < 0.05), respectively, diuresis (5-fold) and natriuresis (2.3-fold) were increased (p < 0.05), and NHE3 activity was significantly reduced, independently of glomerular filtration rate changes. Thus, an acute increase in the BP overcomes RNS, leading to diuresis, natriuresis, and NHE3 activity inhibition.     

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body’s own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016–2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.     

Retrograde Amnesia Induced by Drugs Acting on Different Molecular Systems.

The gamma aminobutyric acid-A (GABAA) agonist, muscimol, the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonopentanoic acid (AP5), and the inhibitor of the extracellularly regulated kinases (ERKs), UO 126, cause retrograde amnesia when administered to the hippocampus. In the present study, the authors found that they all cause retrograde amnesia for 1-trial inhibitory avoidance, not only when infused into the dorsal CA1 region of the hippocampus, but also when infused into the basolateral amygdala or the entorhinal, parietal, and posterior cingulate cortices. The posttraining time course of the effect of each drug was, however, quite different across brain structures. Thus, in all of them, NMDA receptors and the ERK pathway are indispensable for memory consolidation, and GABAA receptor activation inhibits memory consolidation: but in each case, their influence is interwoven differently. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Magnetic Force Microscopy in Liquids

In this work, the use of magnetic force microscopy (MFM) to acquire images of magnetic nanostructures in liquid environments is presented. Optimization of the MFM signal acquisition in liquid media is performed and it is applied to characterize the magnetic signal of magnetite nanoparticles. The ability for detecting magnetic nanostructures along with the well‐known capabilities of atomic force microscopy in liquids suggests potential applications in fields such as nanomedicine, nanobiotechnology, or nanocatalysis.     

TIGUKAT: A uniform behavioral objectbase management system

We describe the TIGUKAT objectbase management system, which is under development at the Laboratory for Database Systems Research at the University of Alberta. TIGUKAT has a novel object model, whose identifying characteristics include a purely behavioral semantics and a uniform approach to objects. Everything in the system, including types, classes, collections, behaviors, and functions, as well as meta-information, is a first-class object with well-defined behavior. In this way, the model abstracts everything, including traditional structural notions such as instance variables, method implementation, and schema definition, into a uniform semantics of behaviors on objects. Our emphasis in this article is on the object model, its implementation, the persistence model, and the query language. We also (briefly) present other database management functions that are under development such as the query optimizer, the version control system, and the transaction manager.Bell Northem Research     

Cytological criteria for assessing the evolution of herpetic keratitis

There were studied 33 patients admitted with clinical diagnosis of superficial herpetic keratitis, typical form of dendritic ulcer. In all these cases there were performed smears from the level of cornea and conjunctiva, that were stained with rapid blue polycrome tanin Dragan staining method. Smears were performed before and during the evolution of the disease, in patients specifically treated with antiviral drugs and also in cases treated unspecifically. There are described some cytological particularities which have a relative specificity for the diagnosis: a high number of lymphocytes with cytoplasmic blebs, giant multinucleated cells, and epithelial cells with degenerative lesions (nucleocytoplasmic inclusions, vacuoles, chromophobe halo around nucleus). Such lesions were not observed in patients with non herpetic keratitis. Modifications noticed in epithelial corneal cells could suggest the diagnosis, which can be associated with clinical examination, in order to administer a specific therapy. Dynamic cytological evolution shows early regression of specific cellular modifications in patients treated by Acyclovir.     

Chlorogenic acids and related compounds in medicinal plants and infusions

The consumption of plant infusions for prevention and treatment of health disorders is a worldwide practise. Various pharmacological activities inherent to medicinal plants have been attributed to their phenolic composition, including chlorogenic acids (CGA). Studies have shown potential beneficial properties of CGA to humans such as antioxidant, hepatoprotective, hypoglycaemic. In the present study, the CGA composition of 14 dried medicinal plants was determined by HPLC-UV and LC-DAD–ESI-MS. The plants with the highest CGA contents were Ilex paraguariensis, Bacharis genistelloides, Pimpinella anisum, Achyrochine satureioides, Camellia sinensis, Melissa officinalis and Cymbopogon citratus, with 84.7 mg/100 g–9.7 g/100 g, dry weight. Plant infusions were prepared (at 0.5%) in order to evaluate the actual consumption of CGA through these beverages. Total CGA contents in the infusions were similar to those in the methanolic extracts and indicated that a satisfactory extraction occurs during the preparation of infusions. These CGA-rich plants deserve attention regarding the pharmacological properties attributed to CGA.     

Involvement of residues 296-299 in the enzymatic activity of tissue-type plasminogen activator

The tetra-alanine substitution variant KHRR 296–299 AAAAof tissue-type plasminogen activator (t-PA) was previously shownto have enhanced fibrin specificity and enhanced activity inthe presence of fibrin compared with the wild-type form of themolecule. The structural requirements for these alterationsin enzymatic activity were investigated by constructing severalamino acid substitution variants at each of the positions from296 to 299 and evaluating their activities under a variety ofconditions. Effects on plasminogen activator activity were commonamong the point mutants at positions 296–299; nearly allhad a phenotype similar to the KHRR 296–299 AAAA variant.The greatest effects on enzymatic function were found with multiplesubstitution variants, but some single charge reversals andproline substitutions had substantial effects. The enhancedfibrin specificity of KHRR 296–299 AAAA t-PA results inless fibrinogenolysis than seen with wild-type t-PA. Approximatelyfour times greater concentration of KHRR 296–299 AAAAcompared with wild-type t-PA was required to consume 50% ofthe fibrinogen in human plasma.     

Biomass estimation in batch biotechnological processes by Bayesian Gaussian process regression

This paper proposes a biomass concentration estimator for a batch biotechnological process based on Bayesian regression with Gaussian process. On the basis of experimental data, a two-stage bootstrap technique has been developed for the estimator design. In the first stage, the biomass data set was augmented with virtual filtered measurements, and in the second stage, the biomass estimator design was completed. The method provides information on the confidence level of the estimates, and the biomass estimator performances are illustrated for the Bacillus thuringiensis δ-endotoxins production process.