The Role of Chemokines in the Development of Gastric Cancer—Diagnostic and Therapeutic Implications

Gastric cancer (GC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. GC is usually diagnosed at an advanced stage due to late presentation of symptoms. Therefore, there is a need for establishing more sensitive and specific markers useful in early detection of the disease when a cancer is asymptomatic to improve the diagnostic and clinical decision-making process. Some researchers suggest that chemokines and their specific receptors play an important role in GC initiation and progression via promotion of angiogenesis, tumor transformation, invasion, survival and metastasis as well as protection from host response and inter-cell communication. Chemokines are small proteins produced by various cells such as endothelial cells, fibroblasts, leukocytes, and epithelial and tumor cells. According to our knowledge, the significance of chemokines and their specific receptors in diagnosing GC and evaluating its progression has not been fully elucidated. The present article offers a review of current knowledge on general characteristics of chemokines, specific receptors and their role in GC pathogenesis as well as their potential usefulness as novel biomarkers for GC.     

Coenzyme Q10: Novel Formulations and Medical Trends

The aim of this review is to shed light over the most recent advances in Coenzyme Q₁₀ (CoQ₁₀) applications as well as to provide detailed information about the functions of this versatile molecule, which have proven to be of great interest in the medical field. Traditionally, CoQ₁₀ clinical use was based on its antioxidant properties; however, a wide range of highly interesting alternative functions have recently been discovered. In this line, CoQ₁₀ has shown pain-alleviating properties in fibromyalgia patients, a membrane-stabilizing function, immune system enhancing ability, or a fundamental role for insulin sensitivity, apart from potentially beneficial properties for familial hypercholesterolemia patients. In brief, it shows a remarkable amount of functions in addition to those yet to be discovered. Despite its multiple therapeutic applications, CoQ₁₀ is not commonly prescribed as a drug because of its low oral bioavailability, which compromises its efficacy. Hence, several formulations have been developed to face such inconvenience. These were initially designed as lipid nanoparticles for CoQ₁₀ encapsulation and distribution through biological membranes and eventually evolved towards chemical modifications of the molecule to decrease its hydrophobicity. Some of the most promising formulations will also be discussed in this review.     

Relation of swelling and Tg depression to the apparent free volume of a particle‐filled,epoxy‐based adhesive

The effect of hygrothermal aging on a particle‐filled, epoxy‐based adhesive was studied using a gravimetric sorption technique. This study has explored moisture sorption characteristics as well as the associated behaviors of swelling and the depression of the glass transition temperature (T_g). We observed that the diffusion of water in this adhesive has a non‐Fickian behavior, and the depression of T_g proceeds to a definite value that is independent of the final equilibrium water content of the system. Our observations suggest that water diffuses into the polymer in a dual‐sorption mode, in which water resides in two populations. In one population, water is considered to occupy apparent free volume of the adhesive, and the second population water infiltrates polymer structure and forms hydrogen‐bonded clusters. Our results show that hygrothermal aging temperature and swelling do not alter the apparent free volume of this adhesive. We conclude that the constant value of T_g depression at saturation implies that only water in the apparent free volume is responsible for the T_g depression, whereas the swelling proceeds through the formation of hydrogen bonds in the adhesive. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1436–1444, 2003     

Non-Intensive Care Unit Acquired Pneumonia: A New Clinical Entity?

Hospital-acquired pneumonia (HAP) is a frequent cause of nosocomial infections, responsible for great morbidity and mortality worldwide. The majority of studies on HAP have been conducted in patients hospitalized in the intensive care unit (ICU), as mechanical ventilation represents a major risk factor for nosocomial pneumonia and specifically for ventilator-associated pneumonia. However, epidemiological data seem to be different between patients acquiring HAP in the ICU vs. general wards, suggesting the importance of identifying non ICU-acquired pneumonia (NIAP) as a clinical distinct entity in terms of both etiology and management. Early detection of NIAP, along with an individualized management, is needed to reduce antibiotic use and side effects, bacterial resistance and mortality. The present article reviews the pathophysiology, diagnosis, treatment and prevention of NIAP.     

Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological,Immunohistochemical and Gene Expression Profiles

Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.     

Influence of Alkaline Additives and Buffers on Mineral Trapping of CO2 under Mild Conditions

Carbon dioxide (CO₂) gas is the main contributor to climate change. CO₂ storage in underground brines and oil‐field brines by mineral trapping has been considered as a promising alternative in order to reduce CO₂ emissions. However, permanent storage of CO₂ in stable carbonate minerals is greatly dependent on brine pH, being favored over an alkaline pH. The effect of alkaline additives (NaOH, KOH, CaO) and buffer solutions (NaHCO₃/NaOH, Na₂HPO₄/NaOH, NH₄Cl/NH₄OH) on the mineral trapping of CO₂ under mild conditions using a synthetic brine is investigated. The results indicate that both NaOH+NH₄Cl/NH₄OH and KOH+NH₄Cl/NH₄OH mixtures promote precipitation mainly of calcium carbonate (CaCO₃).     

Laser‐induced surface structures on gold‐coated polymers: Influence of morphology on surface‐enhanced Raman scattering enhancement

The fabrication of highly sensitive and reproducible substrates for Surface‐Enhanced Raman Scattering (SERS) remains a challenging scientific and technological issue. In this work, laser‐induced periodic surface structures are generated on poly(trimethylen terephthalate) films upon laser irradiation with the linearly polarized beams of a Nd:YAG laser (4th harmonic, 266 nm), an ArF excimer laser (193 nm), and a Titanium:sapphire laser (795 nm), resulting in periods close to the laser wavelength when irradiating at normal incidence, and larger periods for different angles of incidence. Additional irradiation with a circularly polarized beam at 266 nm produces superficial circular structures. The nanostructured polymers are coated with a nanoparticle assembled gold layer by pulsed laser deposition at 213 nm. The capabilities of these substrates for SERS are evaluated using benzenethiol as a test molecule and different degrees of Raman signal enhancement are observed depending on the nanostructure type. The highest enhancement factor is obtained by for nanostructured substrates with the highest values of period, depth, and roughness. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42770.     

Modeling and simulation of an industrial‐scale parex process

The Parex unit for industrial‐scale purification of p‐xylene was studied through detailed simulation and the accuracy of the developed model tested against real industrial data. Starting from a comprehensive analysis of the construction and operation of the industrial unit, a simulation model was developed that incorporates the existing three major types of dead volumes: bed lines, which connect the beds to the rotary valve, circulation lines, which connect adjacent adsorbent chambers, and bed‐head dead volumes, which are located upstream of each bed due to the existence of internals. By gathering operation data and surveys in the pumparound line and in the extract stream, three case studies were defined and compared with simulation results. The model is capable of predicting the performance of the industrial unit. Further simulations were made and compared with plant data to assess the effect of adsorbent capacity loss on the long‐term performance of the unit. © 2015 American Institute of Chemical Engineers AIChE J, 61: 1345–1363, 2015     

Structural Determinants of the Selectivity of 3‐Benzyluracil‐1‐acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10

The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2‐(3‐(4‐chloro‐3‐nitrobenzyl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0048, 3 ) and 2‐(2,4‐dioxo‐3‐(2,3,4,5‐tetrabromo‐6‐methoxybenzyl)‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0049, 4 ), which selectively target these enzymes. Although 3 and 4 share the 3‐benzyluracil‐1‐acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE‐19 cells, whereas 4 stops proliferation in human lung cancer NCI‐H460 cells.     

Next-Generation Sequencing Workflow for NSCLC Critical Samples Using a Targeted Sequencing Approach by Ion Torrent PGM? Platform

Next-generation sequencing (NGS) is a cost-effective technology capable of screening several genes simultaneously; however, its application in a clinical context requires an established workflow to acquire reliable sequencing results. Here, we report an optimized NGS workflow analyzing 22 lung cancer-related genes to sequence critical samples such as DNA from formalin-fixed paraffin-embedded (FFPE) blocks and circulating free DNA (cfDNA). Snap frozen and matched FFPE gDNA from 12 non-small cell lung cancer (NSCLC) patients, whose gDNA fragmentation status was previously evaluated using a multiplex PCR-based quality control, were successfully sequenced with Ion Torrent PGM™. The robust bioinformatic pipeline allowed us to correctly call both Single Nucleotide Variants (SNVs) and indels with a detection limit of 5%, achieving 100% specificity and 96% sensitivity. This workflow was also validated in 13 FFPE NSCLC biopsies. Furthermore, a specific protocol for low input gDNA capable of producing good sequencing data with high coverage, high uniformity, and a low error rate was also optimized. In conclusion, we demonstrate the feasibility of obtaining gDNA from FFPE samples suitable for NGS by performing appropriate quality controls. The optimized workflow, capable of screening low input gDNA, highlights NGS as a potential tool in the detection, disease monitoring, and treatment of NSCLC.