The Glycolytic Pathway as a Target for Novel Onco-Immunology Therapies in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal forms of human cancer, characterized by unrestrained progression, invasiveness and treatment resistance. To date, there are limited curative options, with surgical resection as the only effective strategy, hence the urgent need to discover novel therapies. A platform of onco-immunology targets is represented by molecules that play a role in the reprogrammed cellular metabolism as one hallmark of cancer. Due to the hypoxic tumor microenvironment (TME), PDA cells display an altered glucose metabolism—resulting in its increased uptake—and a higher glycolytic rate, which leads to lactate accumulation and them acting as fuel for cancer cells. The consequent acidification of the TME results in immunosuppression, which impairs the antitumor immunity. This review analyzes the genetic background and the emerging glycolytic enzymes that are involved in tumor progression, development and metastasis, and how this represents feasible therapeutic targets to counteract PDA. In particular, as the overexpressed or mutated glycolytic enzymes stimulate both humoral and cellular immune responses, we will discuss their possible exploitation as immunological targets in anti-PDA therapeutic strategies.     

Searching for Potential Markers of Glomerulopathy in Urine by HS-SPME-GC×GC TOFMS

Volatile organic compounds (VOCs) exiting in urine are potential biomarkers of chronic kidney diseases. Headspace solid phase microextraction (HS-SPME) was applied for extraction VOCs over the urine samples. Volatile metabolites were separated and identified by means of two-dimensional gas chromatography and time of flight mass spectrometry (GC × GC TOF MS). Patients with glomerular diseases (n = 27) and healthy controls (n = 20) were recruited in the study. Different VOCs profiles were obtained from patients and control. Developed methodology offers the opportunity to examine the metabolic profile associated with glomerulopathy. Four compounds found in elevated amounts in the patients group, i.e., methyl hexadecanoate; 9-hexadecen-1-ol; 6,10-dimethyl-5,9-undecadien-2-one and 2-pentanone were proposed as markers of glomerular diseases.     

Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology

DJ-1 was originally identified as an oncogene product while mutations of the gene encoding DJ-1/PARK7 were later associated with a recessive form of Parkinson’s disease. Its ubiquitous expression and diversity of function suggest that DJ-1 is also involved in mechanisms outside the central nervous system. In the last decade, the contribution of DJ-1 to the protection from ischemia-reperfusion injury has been recognized and its involvement in the pathophysiology of cardiovascular disease is attracting increasing attention. This review describes the current and gaps in our knowledge of DJ-1, focusing on its role in regulating cardiovascular function. In parallel, we present original data showing an association between increased DJ-1 expression and antiapoptotic and anti-inflammatory markers following cardiac and vascular surgical procedures. Future studies should address DJ-1’s role as a plausible novel therapeutic target for cardiovascular disease.     

Oxazolidinone Antibiotics: Chemical,Biological and Analytical Aspects

This review covers the main aspects concerning the chemistry, the biological activity and the analytical determination of oxazolidinones, the only new class of synthetic antibiotics advanced in clinical use over the past 50 years. They are characterized by a chemical structure including the oxazolidone ring with the S configuration of substituent at C5, the acylaminomethyl group linked to C5 and the N-aryl substituent. The synthesis of oxazolidinones has gained increasing interest due to their unique mechanism of action that assures high antibiotic efficiency and low susceptibility to resistance mechanisms. Here, the main features of oxazolidinone antibiotics licensed or under development, such as Linezolid, Sutezolid, Eperezolid, Radezolid, Contezolid, Posizolid, Tedizolid, Delpazolid and TBI-223, are discussed. As they are protein synthesis inhibitors active against a wide spectrum of multidrug-resistant Gram-positive bacteria, their biological activity is carefully analyzed, together with the drug delivery systems recently developed to overcome the poor oxazolidinone water solubility. Finally, the most employed analytical techniques for oxazolidinone determination in different matrices, such as biological fluids, tissues, drugs and natural waters, are reviewed. Most are based on HPLC (High Performance Liquid Chromatography) coupled with UV-Vis or mass spectrometer detectors, but, to a lesser extent are also based on spectrofluorimetry or voltammetry.     

Chemical Composition and Potential Practical Application of 15 Red Algal Species from the White Sea Coast (the Arctic Ocean)

Though numerous valuable compounds from red algae already experience high demand in medicine, nutrition, and different branches of industry, these organisms are still recognized as an underexploited resource. This study provides a comprehensive characterization of the chemical composition of 15 Arctic red algal species from the perspective of their practical relevance in medicine and the food industry. We show that several virtually unstudied species may be regarded as promising sources of different valuable metabolites and minerals. Thus, several filamentous ceramialean algae (Ceramium virgatum, Polysiphonia stricta, Savoiea arctica) had total protein content of 20–32% of dry weight, which is comparable to or higher than that of already commercially exploited species (Palmaria palmata, Porphyra sp.). Moreover, ceramialean algae contained high amounts of pigments, macronutrients, and ascorbic acid. Euthora cristata (Gigartinales) accumulated free essential amino acids, taurine, pantothenic acid, and floridoside. Thalli of P. palmata and C. virgatum contained the highest amounts of the nonproteinogenic amino acid β-alanine (9.1 and 3.2 μM g⁻¹ DW, respectively). Several red algae tend to accumulate heavy metals; although this may limit their application in the food industry, it makes them promising candidates for phytoremediation or the use as bioindicators.     

Fluorescent Phthalocyanine-Encapsulated Bovine Serum Albumin Nanoparticles: Their Deployment as Therapeutic Agents in the NIR Region

In recent times, researchers have aimed for new strategies to combat cancer by the implementation of nanotechnologies in biomedical applications. This work focuses on developing protein-based nanoparticles loaded with a newly synthesized NIR emitting and absorbing phthalocyanine dye, with photodynamic and photothermal properties. More precisely, we synthesized highly reproducible bovine serum albumin-based nanoparticles (75% particle yield) through a two-step protocol and successfully encapsulated the NIR active photosensitizer agent, achieving a good loading efficiency of 91%. Making use of molecular docking simulations, we confirm that the NIR photosensitizer is well protected within the nanoparticles, docked in site I of the albumin molecule. Encouraging results were obtained for our nanoparticles towards biomedical use, thanks to their negatively charged surface (−13.6 ± 0.5 mV) and hydrodynamic diameter (25.06 ± 0.62 nm), favorable for benefitting from the enhanced permeability and retention effect; moreover, the MTT viability assay upholds the good biocompatibility of our NIR active nanoparticles. Finally, upon irradiation with an NIR 785 nm laser, the dual phototherapeutic effect of our NIR fluorescent nanoparticles was highlighted by their excellent light-to-heat conversion performance (photothermal conversion efficiency 20%) and good photothermal and size stability, supporting their further implementation as fluorescent therapeutic agents in biomedical applications.     

ICP-MS Assessment of Essential and Toxic Trace Elements in Foodstuffs with Different Geographic Origins Available in Romanian Supermarkets

The present study was conducted to quantify the daily intake and target hazard quotient of four essential elements, namely, chromium, cobalt, nickel, and copper, and four toxic trace elements, mercury, cadmium, lead, and arsenic. Thirty food items were assigned to five food categories (seeds, leaves, powders, beans, and fruits) and analyzed using inductively coupled plasma-mass spectrometry. Factor analysis after principal component extraction revealed common metal patterns in all foodstuffs, and using hierarchical cluster analysis, an association map was created to illustrate their similarity. The results indicate that the internationally recommended dietary allowance was exceeded for Cu and Cr in 27 and 29 foodstuffs, respectively. According to the tolerable upper level for Ni and Cu, everyday consumption of these elements through repeated consumption of seeds (fennel, opium poppy, and cannabis) and fruits (almond) can have adverse health effects. Moreover, a robust correlation between Cu and As (p < 0.001) was established when all samples were analyzed. Principal component analysis (PCA) demonstrated an association between Pb, As, Co, and Ni in one group and Cr, Cu, Hg, and Cd in a second group, comprising 56.85% of the total variance. For all elements investigated, the cancer risk index was within safe limits, highlighting that lifetime consumption does not increase the risk of carcinogens.