Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects

Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%. Non-modifiable (family history, age, genetic susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved in PC pathogenesis. Chronic inflammation induced by various factors plays crucial roles in PC development from initiation to metastasis. In multiple malignant conditions such as PC, cytokines, chemokines, and growth factors activate the class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual inhibitors are being tested in vitro and in vivo with promising results for PC patients. The main aim of this review is to present PC incidence, risk factors, tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and inhibitors used in clinical, in vivo, and in vitro studies.     

Studies on the Detection of Oleuropein from Extra Virgin Olive Oils Using Enzymatic Biosensors

Oleuropein (OLEU) is an important indicator of the quality and authenticity of extra virgin olive oils (EVOO). Electrochemical sensors and biosensors for the detection of oleuropein can be used to test the adulteration of extra virgin olive oils. The present study aimed at the qualitative and quantitative determination of oleuropein in commercial EVOO samples by applying electrochemical techniques, cyclic voltammetry (CV) and square wave voltammetry (SWV). The sensing devices used were two newly constructed enzyme biosensors, supported on single-layer carbon-nanotube-modified carbon screen-printed electrode (SPE/SWCNT) on whose surface tyrosinase (SPE/SWCNT/Tyr) and laccase (SPE/SWCNT/Lac) were immobilized, respectively. The active surfaces of the two biosensors were analyzed and characterized by different methods, cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and Fourier transform infrared spectroscopy (FTIR) and the results confirmed the efficient immobilization of the enzymes. SPE/SWCNT/Tyr was characterized by a low detection limit (LOD = 9.53 × 10⁻⁸ M) and a very good sensitivity (0.0718 μA·μM⁻¹·cm⁻²) over a wide linearity range from 0.49 to 11.22 μM. The process occurring at the biosensor surface corresponds to kinetics (h = 0.90), and tyrosinase showed a high affinity towards OLEU. The tyrosinase-based biosensor was shown to have superior sensitive properties to the laccase-based one. Quantitative determination of OLEU in EVOOs was performed using SPE/SWCNT/Tyr and the results confirmed the presence of the compound in close amounts in the EVOOs analysed, proving that they have very good sensory properties.     

Biomarkers in Systemic Juvenile Idiopathic Arthritis,Macrophage Activation Syndrome and Their Importance in COVID Era

Systemic juvenile idiopathic arthritis (sJIA) and its complication, macrophage activation syndrome (sJIA-MAS), are rare but sometimes very serious or even critical diseases of childhood that can occasionally be characterized by nonspecific clinical signs and symptoms at onset—such as non-remitting high fever, headache, rash, or arthralgia—and are biologically accompanied by an increase in acute-phase reactants. For a correct positive diagnosis, it is necessary to rule out bacterial or viral infections, neoplasia, and other immune-mediated inflammatory diseases. Delays in diagnosis will result in late initiation of targeted therapy. A set of biomarkers is useful to distinguish sJIA or sJIA-MAS from similar clinical entities, especially when arthritis is absent. Biomarkers should be accessible to many patients, with convenient production and acquisition prices for pediatric medical laboratories, as well as being easy to determine, having high sensitivity and specificity, and correlating with pathophysiological disease pathways. The aim of this review was to identify the newest and most powerful biomarkers and their synergistic interaction for easy and accurate recognition of sJIA and sJIA-MAS, so as to immediately guide clinicians in correct diagnosis and in predicting disease outcomes, the response to treatment, and the risk of relapses. Biomarkers constitute an exciting field of research, especially due to the heterogeneous nature of cytokine storm syndromes (CSSs) in the COVID era. They must be selected with utmost care—a fact supported by the increasingly improved genetic and pathophysiological comprehension of sJIA, but also of CSS—so that new classification systems may soon be developed to define homogeneous groups of patients, although each with a distinct disease.     

Stimulatory Effect of Lactobacillus Metabolites on Colonic Contractions in Newborn Rats

Microbiota are known to play an important role in gastrointestinal physiology and pathophysiology. Microbiota and their metabolites can affect gut motility, neural regulation and the enteric endocrine systems and immune systems of the gut. The use of fermented/hydrolyzed products may be a promising new avenue for stimulating gastrointestinal motility. The purpose of this study was to investigate the effect of lactobacillus metabolites (PP), produced using a U.S.-patented fermentation method, on rat colon motility in vitro. The distal colon was incised from newborn male Wistar rats. A sensitive tensometric method for the study of colon contractions was used. The [Ca²⁺]_i in colon tissue was registered using a computerized ratiometric system for an intracellular ion content assay (Intracellular Imaging and Photometry System, Intracellular imaging, Inc. Cincinnati, OH, USA). The cumulative addition of PP induced contraction with sigmoid dose responses with ED₅₀ = 0.13 ± 0.02% (n = 4), where 10% PP was accepted as a maximal dose. This contraction was accompanied by an increase in the concentration of [Ca²⁺]_i. It was shown that introducing Lactobacillus metabolites produced using a U.S.-patented fermentation method quickly stimulates dose-dependent colon contractions and an increase in intracellular calcium. The direct application of PP via enema to the colon could stimulate colon motility and suppress pathogenic microbiota, owing to the antagonistic property of PP on pathogens.     

Increased sensibility of mixed ferrite humidity sensors by subsequent heat treatment

The study presents the effects of different calcination temperatures on the size and morphology of mixed Co‐Ni ferrites, and the respective changes in the magnetic and electrical properties, with emphasis on their applicability as humidity sensors. The data suggests that the heat treatment does not significantly change the magnetic properties, but significant variations on the morphology of the nanoparticles, correlated with large changes in the electrical properties of the nanoparticles in terms of electrical permittivity and resistivity with electrical field frequency and humidity, with a clear influence of the calcination temperature over the sensibility of the materials to humidity.     

Structure and enzymatic activity of laser immobilized ribonuclease A

Ribonuclease A (RNase A) enzyme was immobilized on solid holders by matrix-assisted pulsed laser evaporation (MAPLE) technique. The experiments were performed inside a stainless steel irradiation chamber. A UV KrF* (λ = 248 nm, τ_FWHM ? 25 ns, ν = 10 Hz) excimer laser source was used for irradiations. Surface morphology, molecular structure, and enzymatic activity of laser transferred RNase A samples were investigated as a function of RNase A concentration in the frozen composite MAPLE targets. Surface morphology and thickness of the immobilized enzyme were investigated by atomic force microscopy, scanning electron microscopy, and surface profilometry. The molecular structure of the laser transferred RNase A was determined by Fourier transform infrared spectroscopy. The enzymatic activity of RNase A after immobilization was tested through ribonucleic acid removal from deoxyribonucleic acid (DNA) extract solutions isolated from plant and animal tissues. A molecular method based on polymerase chain reaction was used to investigate the functional properties of DNA extracts treated with laser immobilized RNase A.     

Inhibition effect of some aromatic amines on copper electrodeposition from acidic baths

To improve the quality requirements for copper deposits, the influence of some inhibition agents added to the acidic copper bath has been studied. Several aromatic nitrogen compounds have been tested as inhibition agents, such as aniline, N-methylaniline, N-ethylaniline, N,N-dimethylaniline (DMA), and N,N-diethylaniline (DEA). The electrochemical behavior of these organic additives and the most relevant aspects of the electrochemical behavior of copper in acid solutions have been analyzed by cyclic voltammetry. At the same time, a correlation between voltammetric data and molecular properties of protonated amines obtained by molecular modeling has been performed. The morphology of the copper deposits obtained in the absence and presence of organic compounds has been studied by scanning electron microscopy. An improvement of the roughness degree and crystallite size upon addition of aromatic amine has been found. Best results were obtained for DMA and DEA working at room temperature (25 ± 0.1 °C) and 200 A m⁻² current density, in 1 mol L⁻¹ sulfuric acid solution with 50 g L⁻¹ Cu²⁺.     

Environmental impact assessment of green energy systems for power supply of electric vehicle charging station

The Electric Vehicle (EV) as a clean alternative to Classic Vehicle that use fossil fuels is promoted as an immediate solution to improve the quality parameters of the environment related to the transport sector. The transition to clean electrified mobility must be considered from the sustainability spectrum, and the planning of a strategy related to the implementation of electric vehicles implies, from the beginning, providing clean energy conditions to go toward a green-to-green paradigm. It should be noted that the successful implementation of the “green electro mobility” concept depends heavily on the green energy supply solutions of green electric vehicle, so Electric Vehicle Charging Stations (EV-CS) should be powered by electricity generation systems based on green resources. This research article has as main objective the environmental impact assessment from the perspective of CO₂ emissions embedded in green stand-alone energy systems and the estimation of the environmental benefits of their implementation in the power supply of EV-CS from the perspective of avoided CO₂ emissions compared to the classic electricity supply grid. The results indicate that the green energy systems represent feasible solutions for the independent energy support of electric vehicle charging stations, being able to supply electricity based on on-site available 100% alternative energy sources. Related to 1 kWh of electricity, the CO₂ emissions embedded in these systems represent on average 11.40% of the CO₂ emissions of the electricity supplied through the grid at European level and on average 7.10% of the CO₂ emissions of the electricity supplied through the grid worldwide. Results also show that the average price of 1kWh of electricity generated by the analyzed systems is 4.3 times higher than the average unit price of the European Union grid energy, but this indicator must be correlated with the kgCO₂/kWh cost savings compared to the electricity production from classic power plants.