The Effects of the Steroids 5-Androstenediol and Dehydroepiandrosterone and Their Synthetic Derivatives on the Viability of K562, HeLa, and Wi-38 Cells and the Luminol-Stimulated Chemiluminescence of Peripheral Blood Mononuclear Cells from Healthy Volunteers.

In order to evaluate the role of substituents at 3-C and 17-C in the cytotoxic and cytoprotective actions of DHEA and 5-AED molecules, their derivatives were synthesized by esterification using the corresponding acid anhydrides or acid chlorides. As a result, seven compounds were obtained: four DHEA derivatives (DHEA 3-propionate, DHEA 3-butanoate, DHEA 3-acetate, DHEA 3-methylsulfonate) and three 5-AED derivatives (5-AED 3-butanoate, 5-AED 3,17-dipropionate, 5-AED 3,17-dibutanoate). All of these compounds showed micromolar cytotoxic activity toward HeLa and K562 human cancer cells.

as a Rapid Screening Model to Evaluate the Hypoglycemic Effects of Dipeptidyl Peptidase 4 (DPP4) Inhibitors: High Evolutionary Conservation of DPP4.

Dipeptidyl peptidase 4 (DPP4) inhibitors, commonly known as gliptins, have been an integral part of the treatment of type 2 diabetes mellitus (T2DM) for several years. Despite their remarkable efficacy in lowering glucose levels and their compatibility with other hypoglycemic drugs, recent studies have revealed adverse effects, prompting the search for improved drugs within this category, which has required the use of animal models to verify the hypoglycemic effects of these compounds. Currently, in many countries the use of mammals is being significantly restricted, as well as cost prohibitive, and alternative in vivo approaches have been encouraged.

Triple drug therapy with GABA, sitagliptin, and omeprazole prevents type 1 diabetes onset and promotes its reversal in non-obese diabetic mice.

Previous studies have reported that dual drug combinations consisting of γ-aminobutyric acid (GABA) together with a dipeptidyl-peptidase-4 inhibitor (DPP-4i), also a DPP-4i with a proton pump inhibitor (PPI), could improve pancreatic β-cell function and ameliorate diabetes in diabetic mice. In this study, we sought to determine if a triple drug combination of GABA, a DPP-4i and a PPI might have superior therapeutic effects compared with double drug therapies in the prevention and reversal of diabetes in the non-obese diabetic (NOD) mouse model of human type 1 diabetes (T1D). In a diabetes prevention arm of the study, the triple drug combination of GABA, a DPP-4i, and a PPI exhibited superior therapeutic effects in preventing the onset of diabetes compared with all the double drug combinations and placebo.

Effect of artifacts upon the pressure reactivity index.

The pressure reactivity index (PRx) is a parameter for the assessment of cerebrovascular autoregulation, but its calculation is affected by artifacts in the source biosignals-intracranial pressure (ICP) and arterial blood pressure. We sought to describe the most common short-duration artifacts and their effect on the PRx. A retrospective analysis of 935 h of multimodal monitoring data was conducted, and five types of artifacts, characterized by their shape, duration, and amplitude, were identified: rectangular, fast impulse, isoline drift, saw tooth, and constant ICP value.

Design, Synthesis and Biological Evaluation of Neogliptin, a Novel 2-Azabicyclo[2.2.1]heptane-Based Inhibitor of Dipeptidyl Peptidase-4 (DPP-4).

Compounds that contain (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid substituted with bicyclic amino moiety (2-aza-bicyclo[2.2.1]heptane) were designed using molecular modelling methods, synthesised, and found to be potent DPP-4 (dipeptidyl peptidase-4) inhibitors.

Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales.

Type 2 diabetes mellitus (T2DM) continues to be a substantial medical problem due to its increasing global prevalence and because chronic hyperglycemic states are closely linked with obesity, liver disease and several cardiovascular diseases. Since the early discovery of insulin, numerous antihyperglycemic drug therapies to treat diabetes have been approved, and also discontinued, by the United States Food and Drug Administration (FDA). To provide an up-to-date account of the current trends of antidiabetic pharmaceuticals, this review offers a comprehensive analysis of the main classes of antihyperglycemic compounds and their mechanisms: insulin types, biguanides, sulfonylureas, meglitinides (glinides), alpha-glucosidase inhibitors (AGIs), thiazolidinediones (TZD), incretin-dependent therapies, sodium-glucose cotransporter type 2 (SGLT2) inhibitors and combinations thereof.

Green Enabling Technologies for Competitive Synthesis of Pharmaceutical Lead Compounds.

Combinations of different technologies are at the heart of the development and implementation of new, innovative processes and approaches for Industry 4.0 in the field of medicinal chemistry and drug discovery. Process intensification and advances in high-throughput synthetic techniques can dramatically improve reaction rates in processes for which slow kinetics represents a bottleneck.

Correction to: Draft genome sequences of Hirudo medicinalis and salivary transcriptome of three closely related medicinal leeches.

An amendment to this paper has been published and can be accessed via the original article.

Draft genome sequences of Hirudo medicinalis and salivary transcriptome of three closely related medicinal leeches.

Background: Salivary cell secretion (SCS) plays a critical role in blood feeding by medicinal leeches, making them of use for certain medical purposes even today.

Results: We annotated the Hirudo medicinalis genome and performed RNA-seq on salivary cells isolated from three closely related leech species, H. medicinalis, Hirudo orientalis, and Hirudo verbana.

Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements.

In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients' prognosis. It was widely demonstrated that through the non-invasive analysis of ctDNA, it is possible to identify and characterize the mutational status of tumors while avoiding invasive diagnostic strategies. Although a number of studies on ctDNA in patients' samples significantly contributed to the improvement of oncology practice, some investigations generated conflicting data about the diagnostic and prognostic significance of ctDNA.

Medicinal leech antimicrobial peptides lacking toxicity represent a promising alternative strategy to combat antibiotic-resistant pathogens.

The rise of antibiotic resistance has necessitated the development of alternative strategies for the treatment of infectious diseases. Antimicrobial peptides (AMPs), components of the innate immune response in various organisms, are promising next-generation drugs against bacterial infections. The ability of the medicinal leech Hirudo medicinalis to store blood for months with little change has attracted interest regarding the identification of novel AMPs in this organism.

Spectroscopy of the Surface Polaritons in the CdZnP Solid Solutions.

Here we report on the analysis of the effect of the doping of CdP single crystals by ZnP nanoclusters on the dispersion of the surface polaritons (SP). The ATR spectroscopic technique has been applied to excite the SP in the CdZnP system. Analysis of the obtained spectra has shown that the doping of CdP single crystals by ZnP nanoclusters result in the position and the width of the dispersion branches of the SP.

The Role of ZnP2 Nanoclusters in the Vibrational Properties of Cd x Zn(1 - x)P2 Solid Solutions.

This study reports an analysis of the IR reflectance and Raman spectra of Cd x Zn(1 - x)P2 solid solutions. We have analyzed the effect of the doping of the CdP2 single crystal by the ZnP2 nanoclusters on the vibrational properties of studied samples: ε 0, ε inf, phonon frequencies, and strengths. These dependencies might be used as an alternative non-destructive way for the control of the Cd x Zn(1 - x)P2 composition.

Pressure control of magnetic clusters in strongly inhomogeneous ferromagnetic chalcopyrites.

Room-temperature ferromagnetism in Mn-doped chalcopyrites is a desire aspect when applying those materials to spin electronics. However, dominance of high Curie-temperatures due to cluster formation or inhomogeneities limited their consideration. Here we report how an external perturbation such as applied hydrostatic pressure in CdGeP₂:Mn induces a two serial magnetic transitions from ferromagnet to non-magnet state at room temperature.

Tetranuclear iron(III) complexes of an octadentate pyridine-carboxylate ligand and their catalytic activity in alkane oxidation by hydrogen peroxide.

Reaction of the octadentate ligand 2,6-bis{3-[N,N-di(2-pyridylmethyl)amino]propoxy}benzoic acid (LH) with Fe(ClO4)3 leads to the formation of the tetranuclear complexes [Fe4(mu-O)2(LH)2(ClCH2-CO2)4](ClO4)4 (1), [{Fe2(mu-O)L(R-CO2)}2](ClO4)4 (2 R = C6H5-, 3 R = CH3-, 4, R = ClCH2-). The crystal structures of complexes 1 and 2 reveal that they consist of two Fe(III)2(mu-O)(mu-RCO2)2 cores that are linked via the two LH/L ligands to give a "dimer of dimers" structure. Complex assumes a helical shape, with protonated carboxylic acid moieties of the two ligands forming a hydrogen-bonded pair at the center of the cation.

Design and synthesis of new models for diiron biosites.

In order to mimic dinuclear active sites of some non-heme diiron proteins, ten new polydentate and potentially dinucleating ligands have been synthesized. Each ligand contains a carboxylate moiety designed to bridge two metal atoms. These central carboxylate moieties are derived from substituted benzoic acids that in turn are linked to terminal nitrogen or oxygen donors by spacers so that framework-type polydentate ligands similar to the polypeptide frames in diiron metallobiosites are formed.