Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients’ prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones’ survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host’s immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.     

Inactivation of Enterobacter sakazakii by pulsed electric field in buffered peptone water and infant formula milk

The effect of high-intensity pulsed electric field (PEF) treatment on the survival of Enterobacter sakazakii suspended in buffered peptone water (BPW) and powdered infant formula milk (IFM) was evaluated. Reference medium and IFM samples were treated with PEF. Electric field intensity and treatment time were varied from 10 to 40 kV cm⁻¹ and from 60 to 3895 μs, respectively. Samples of buffered peptone water (3 g L⁻¹) and IFM were inoculated with E. sakazakii (CECT 858) (10⁹ cfu mL⁻¹) and then treated with PEF. The inactivation data were adjusted to the Weibull frequency distribution function and Bigelow model, and constants were calculated for both substrates. A maximum 2.7 log (cfu mL⁻¹) reduction was achieved in BPW after exposure of E. sakazakii to PEF for 360 μs (2.5 μs pulse width) at 40 kV cm⁻¹. In IFM, exposure of E. sakazakii to PEF, with the same conditions, led to a 1.2 log (cfu mL⁻¹) reduction. The greater the field strength and treatment time, the greater the inactivation achieved in both substrates. Even though further research will be necessary, according to the results, there are good prospects for the use of PEF in hospitals to achieve safe reconstituted infant formula before storage at refrigerated temperatures.     

Applications of Plasma-Activated Water in Dentistry: A Review

The activation of water by non-thermal plasma creates a liquid with active constituents referred to as plasma-activated water (PAW). Due to its active constituents, PAW may play an important role in different fields, such as agriculture, the food industry and healthcare. Plasma liquid technology has received attention in recent years due to its versatility and good potential, mainly focused on different health care purposes. This interest has extended to dentistry, since the use of a plasma–liquid technology could bring clinical advantages, compared to direct application of non-thermal atmospheric pressure plasmas (NTAPPs). The aim of this paper is to discuss the applicability of PAW in different areas of dentistry, according to the published literature about NTAPPs and plasma–liquid technology. The direct and indirect application of NTAPPs are presented in the introduction. Posteriorly, the main reactors for generating PAW and its active constituents with a role in biomedical applications are specified, followed by a section that discusses, in detail, the use of PAW as a tool for different oral diseases.     

Strain-specific polyketide synthase genes of Aspergillus niger

In silico comparison of 34 putative pks genes in Aspergillus niger strain CBS 513.88 versus A. niger strain ATCC 1015 genome revealed significant nucleotide identity (>95% covering a minimum of 99% of the gene sequence) for 31 of these genes (approximately 91%). A. niger CBS 513.88 harbors three putative pks genes (An01g01130, An11g05940, and An15g07920), for which nucleotide identity was not found in A. niger ATCC 1015. To compare the results of the in silico analysis with the in vivo situation, experimental data were obtained for a large number of A. niger strains obtained from different substrates and geographical regions. Three putative pks genes that were found to be variable between the two A. niger strains using bioinformatics tools were in fact strain-specific genes based on experimental data. The PCR amplification signals for the An01g01130, An11g05940, and An15g07920 pks genes were detected in only 97%, 71%, and 26% of the strains, respectively. Southern blot analyses confirmed the PCR data. Because one of the strain-specific pks genes (An15g07920) is located in a putative ochratoxin cluster, we focused our investigation on that region. We assessed the ochratoxin production capability of the 119 A. niger strains and found a positive association between the presence of this pks gene and the capability of the respective strain to produce ochratoxin.     

Biogenic Amines Formation in Bigeye Tuna Steaks and Whole Skipjack Tuna

ABSTRACT: Putrescine, cadaverine and histamine formation was monitored in fresh and frozen/thawed Bigeye tuna steaks ( Thunnus obesus ) and whole Skipjack ( Katsuwonus pelamis ) stored at room temperature and in ice and to determine the potential use of putrescine and cadaverine as indicators of decomposition. While all biogenic amines were formed during both storage conditions, putrescine was formed at a much lower rate and concentration. For both storage conditions and species, cadaverine appeared prior to and/or accumulated at a faster rate than histamine. Skipjack tuna had a faster accumulation of cadaverine than Bigeye under the same storage conditions. The results indicated that cadaverine, either alone or with histamine, could be used as an index of decomposition for Skipjack and Bigeye tuna.     

Pressure inactivation kinetics of Enterobacter sakazakii in infant formula milk

Survival curves of Enterobacter sakazakii inactivated by high hydrostatic pressure were obtained at four pressure levels (250, 300, 350, and 400 MPa), at temperatures below 30 degrees C, in buffered peptone water (BPW; 0.3%, wt/vol) and infant formula milk (IFM; 16%, wt/vol). A linear model and four nonlinear models (Weibull, log-logistic, modified Gompertz, and Baranyi) were fitted to the data, and the performances of the models were compared. The linear regression model for the survival curves in BPW and IFM at 250 MPa has fitted regression coefficient (R2) values of 0.940 to 0.700, respectively, and root mean square errors (RMSEs) of 0.770 to 0.370. For the other pressure levels, the linear regression function was not appropriate, as there was a strong curvature in the plotted data. The nonlinear regression models with the log-logistic and modified Gompertz equations had R2 values of 0.960 to 0.992 and RMSE values of 0.020 to 0.130 within pressure levels of 250 to 400 MPa, respectively. These results indicate that they are both better models for describing the pressure inactivation kinetics of E. sakazakii in IFM and BPW than the Weibull distribution function, which has an R2 minimum value of 0.832 and an RMSE maximum value of 0.650 at 400 MPa. On the other hand, the parameters for the Weibull distribution function, log-logistic model, and modified Gompertz equation did not have a clear dependence on pressure. The Baranyi model was also analyzed, and it was concluded that this model provided a reasonably good fit and could be used to develop predictions of survival data at pressures other than the experimental pressure levels in the range studied. The results provide accurate predictions of survival curves at different pressure levels and will be beneficial to the food industry in selecting optimum combinations of pressure and time to obtain desired target levels of E. sakazakii inactivation in IFM.     

Blood Thiol Redox State in Chronic Kidney Disease

Thiols (sulfhydryl groups) are effective antioxidants that can preserve the correct structure of proteins, and can protect cells and tissues from damage induced by oxidative stress. Abnormal levels of thiols have been measured in the blood of patients with moderate-to-severe chronic kidney disease (CKD) compared to healthy subjects, as well as in end-stage renal disease (ESRD) patients on haemodialysis or peritoneal dialysis. The levels of protein thiols (a measure of the endogenous antioxidant capacity inversely related to protein oxidation) and S-thiolated proteins (mixed disulphides of protein thiols and low molecular mass thiols), and the protein thiolation index (the molar ratio of the S-thiolated proteins to free protein thiols in plasma) have been investigated in the plasma or red blood cells of CKD and ESRD patients as possible biomarkers of oxidative stress. This type of minimally invasive analysis provides valuable information on the redox status of the less-easily accessible tissues and organs, and of the whole organism. This review provides an overview of reversible modifications in protein thiols in the setting of CKD and renal replacement therapy. The evidence suggests that protein thiols, S-thiolated proteins, and the protein thiolation index are promising biomarkers of reversible oxidative stress that could be included in the routine monitoring of CKD and ESRD patients.     

A Modular Composite Device of Poly(Ethylene Oxide)/Poly(Butylene Terephthalate) (PEOT/PBT) Nanofibers and Gelatin as a Dual Drug Delivery System for Local Therapy of Soft Tissue Tumors

In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel–electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds’ characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermore, publicly available expression datasets were interrogated. Confocal imaging showcased the nontoxicity of these devices in vitro. ELISA assays confirmed a modulation of IL-10 inflammation-related cytokine supporting the role of this device in tissue repair. In silico analysis confirmed the role of IL-10 in solid tumors including 262 patients affected by sarcoma as a negative prognostic marker for overall survival. In conclusion, the developed modular composite device may provide a key-enabling technology for the treatment of soft tissue sarcoma.     

Polyetherimide-LaNi5 composite films for hydrogen storage applications

This study investigates the preparation of polyetherimide (PEI) – LaNi₅ composites films for hydrogen storage. Prior to the polymer addition, LaNi₅ was ball-milled at different conditions (250, 350, and 450 RPM) and annealed at 500 °C for 1 h under vacuum. The composites were produced with BM-LaNi₅-350 (PEI/LaNi₅-350) and annealed BM-LaNi₅-350 (PEI/LaNi₅-350-TT). Membranes were successfully produced through solvent casting assisted by an ultrasonic bath. The particles dispersion and the film morphology did not change after hydrogenation cycles. In the H₂ sorption experiments at 43 °C and 20 bar, the films stored H₂ without incubation time; both samples reached a capacity of ~0.6 wt%. The H₂ sorption kinetics of PEI/LaNi₅-350 was comparable to that of BM-LaNi₅-350, whereas PEI/LaNi₅-350-TT presented significantly slower kinetics. LaNi₅ oxidation was hindered by PEI, showing that it can be explored to improve metal hydrides air resistance. The results demonstrated that PEI films filled with LaNi₅ are promising materials for hydrogen storage.     

A GC-EI-MS/MS Method for the Determination of 15 Polybrominated Diphenyl Ethers (PBDEs) in Fish and Shellfish Tissues

This paper describes the development and validation of an analytical method to determine 15 polybrominated diphenyl ethers (PBDEs) in fish and shellfish tissues with gas chromatography coupled to triple quadrupole mass spectrometry using electron impact source (GC-EI-MS/MS). A QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe)-like procedure was applied; the extract was cleaned up on an acidic Extrelut-NT3 column connected on top of a silica cartridge and further purified with gel permeation chromatography (GPC). The SIM acquisition proved to yield better results than traditional MRM approach for octa-, nona-, and deca-brominated congeners. The validation study was carried out in inter-laboratory conditions. The average recoveries were in the range 66–118%, with relative standard deviations generally lower than or equal to 22%. Quality assurance and quality control practices were thoroughly described and highlighted. These long and tedious practices are fundamental to obtain reliable quantitative data during food monitoring programs and, therefore, to support daily intake assessments. Finally, the procedure was applied to the analysis of marine fish samples collected in local markets. Mackerel and mullet were the most contaminated species.