Effects of Non-Opioid Analgesics on the Cell Membrane of Skin and Gastrointestinal Cancers

Skin and gastrointestinal cancer cells are the target of research by many scientists due to the increasing morbidity and mortality rates around the world. New indications for drugs used in various conditions are being discovered. Non-opioid analgesics are worth noting as very popular, widely available, relatively cheap medications. They also have the ability to modulate the membrane components of tumor cells. The aim of this review is to analyze the impact of diclofenac, ibuprofen, naproxen, acetylsalicylic acid and paracetamol on skin and gastrointestinal cancers cell membrane. These drugs may affect the membrane through topical application, at the in vitro and in vivo level after oral or parenteral administration. They can lead to up- or downregulated expression of receptors, transporters and other molecules associated with plasma membrane. Medications may also alter the lipid bilayer composition of membrane, resulting in changes in its integrity and fluidity. Described modulations can cause the visualization of cancer cells, enhanced response of the immune system and the initiation of cell death. The outcome of this is inhibition of progression or reduction of tumor mass and supports chemotherapy. In conclusion, non-opioid analgesics may be used in the future as adjunctive therapy for the treatment of these cancers.     

Biomarkers for the Diagnosis of Alzheimer’s Disease in Clinical Practice: The Role of CSF Biomarkers during the Evolution of Diagnostic Criteria

Alzheimer’s disease (AD) is a progressive condition and the most common cause of dementia worldwide. The neuropathological changes characteristic of the disorder can be successfully detected before the development of full-blown AD. Early diagnosis of the disease constitutes a formidable challenge for clinicians. CSF biomarkers are the in vivo evidence of neuropathological changes developing in the brain of dementia patients. Therefore, measurement of their concentrations allows for improved accuracy of clinical diagnosis. Moreover, AD biomarkers may provide an indication of disease stage. Importantly, the CSF biomarkers of AD play a pivotal role in the new diagnostic criteria for the disease, and in the recent biological definition of AD by the National Institute on Aging, NIH and Alzheimer’s Association. Due to the necessity of collecting CSF by lumbar puncture, the procedure seems to be an important issue not only from a medical, but also a legal, viewpoint. Furthermore, recent technological advances may contribute to the automation of AD biomarkers measurement and may result in the establishment of unified cut-off values and reference limits. Moreover, a group of international experts in the field of AD biomarkers have developed a consensus and guidelines on the interpretation of CSF biomarkers in the context of AD diagnosis. Thus, technological advancement and expert recommendations may contribute to a more widespread use of these diagnostic tests in clinical practice to support a diagnosis of mild cognitive impairment (MCI) or dementia due to AD. This review article presents up-to-date data regarding the usefulness of CSF biomarkers in routine clinical practice and in biomarkers research.     

Gene Variants Related to Cardiovascular and Pulmonary Diseases May Correlate with Severe Outcome of COVID-19

Background: Severe outcomes of COVID-19 account for up to 15% of all cases. The study aims to check if any gene variants related to cardiovascular (CVD) and pulmonary diseases (PD) are correlated with a severe outcome of COVID-19 in a Polish cohort of COVID-19 patients. Methods: In this study, a subset of 747 samples from unrelated individuals collected across Poland in 2020 and 2021 was used and whole-genome sequencing was performed. Results: The GWAS analysis of SNPs and short indels located in genes related to CVD identified one variant significant in COVID-19 severe outcome in the HADHA gene, while for the PD gene panel, we found two significant variants in the DRC1 gene. In this study, both potentially protective and risk variants were identified, of which variants in the HADHA gene deserve the most attention. Conclusions: This is the first study reporting the association between the HADHA and DRC1 genetic variants and COVID-19 severe outcome based on the cohort WGS analysis. Although all the identified variants are localised in introns, they may be correlated and therefore inherited along with other risk variants, potentially causative to severe outcome of COVID-19 but not discovered yet.     

Enapotamab Vedotin,an AXL-Specific Antibody-Drug Conjugate,Demonstrates Antitumor Efficacy in Patient-Derived Xenograft Models of Soft Tissue Sarcoma

Doxorubicin (doxo) remains the standard of care for patients with advanced soft tissue sarcoma (STS), even though response rates to doxo are only around 14% to 18%. We evaluated enapotamab vedotin (EnaV), an AXL-specific antibody-drug conjugate (ADC), in a panel of STS patient-derived xenografts (PDX). Eight models representing multiple STS subtypes were selected from our STS PDX platform (n = 45) by AXL immunostaining on archived passages. Models were expanded by unilateral transplantation of tumor tissue into the left flank of 20 NMRI nu/nu mice. Once tumors were established, mice were randomized into an EnaV treatment group, or a group treated with isotype control ADC. Treatment efficacy was assessed by tumor volume evaluation, survival analysis, and histological evaluation of tumors, and associated with AXL expression. EnaV demonstrated significant tumor growth delay, regression, and/or prolonged survival compared to isotype control ADC in 5/8 STS PDX models investigated. Experimental passages of responding models were all found positive for AXL at varying levels, but no linear relationship could be identified between the level of expression and level of response to EnaV. One model was found negative for AXL on experimental passage and did not respond to EnaV. This study provides a preclinical rationale for the evaluation of AXL-targeting ADCs in the treatment of AXL-expressing sarcomas.     

Evaluation of the Effects of Ag,Cu, ZnO and TiO2 Nanoparticles on the Expression Level of Oxidative Stress-Related Genes and the Activity of Antioxidant Enzymes in Escherichia coli,Bacillus cereus and Staphylococcus epidermidis

Although the molecular response of bacteria exposed to metal nanoparticles (NPs) is intensively studied, many phenomena related to their survival, metal uptake, gene expression and protein production are not fully understood. Therefore, this work aimed to study Ag-NPs, Cu-NPs, ZnO-NPs and TiO₂-NPs-induced alterations in the expression level of selected oxidative stress-related genes in connection with the activity of antioxidant enzymes: catalase (CAT), peroxidase (PER) and superoxide dismutase (SOD) in Escherichia coli, Bacillus cereus and Staphylococcus epidermidis. The methodology used included: the extraction of total RNA and cDNA synthesis, the preparation of primers for selected housekeeping and oxidative stress genes, RT-qPCR reaction and the measurements of CAT, PER and SOD activities. It was established that the treatment of E. coli and S. epidermidis with NPs resulted mainly in the down-regulation of targeted genes, whilst the up-regulation of genes was confirmed in B. cereus. The greatest differences in the relative expression levels of tested genes occurred in B. cereus and S. epidermidis treated with TiO₂-NPs, while in E. coli, they were observed under ZnO-NPs exposure. The changes found were mostly related to the expression of genes encoding proteins with PER and CAT-like activity. Among NPs, ZnO-NPs and Cu-NPs increased the activity of antioxidants in E. coli and B. cereus. In turn, TiO₂-NPs had a major effect on enzymes activity in S. epidermidis. Considering all of the collected results for tested bacteria, it can be emphasised that the impact of NPs on the antioxidant system functioning was dependent on their type and concentration.     

Effects of carbonate on the electrolytic removal of ammonia and urea from urine with thermally prepared IrO<Subscript>2</Subscript> electrodes

Recent studies have shown that electrolysis can be an efficient process for nitrogen removal from urine. These studies have been conducted with urea solutions or fresh urine, but urine collected in NoMix toilets and urinals has a substantially different composition, because bacteria hydrolyse urea quickly to ammonia and carbonate. In this study, we compared electrochemical removal of nitrogen from synthetic solutions of fresh and stored urine using IrO₂ anodes. We could show that in fresh urine both ammonia and urea are efficiently eliminated, mainly through chlorine-mediated oxidation. However, in stored urine the presence of carbonate, arising from urea hydrolysis, leads to an inhibition of ammonia oxidation. We suggest two parallel mechanisms to explain this effect: the competition between chloride and carbonate oxidation at the anode and the competition between chlorate formation, enhanced by the buffering effect of carbonate, and ammonia oxidation for the consumption of active chlorine in the bulk. However, further experiments are needed to support the latter mechanism. In conclusion, this study highlights the negative consequences of the presence of carbonate in urine solutions, but also in other wastewaters, when subjected to an electrolytic treatment on IrO₂ in alkaline media.     

Effect of muscle,ageing time and modified atmosphere packaging conditions on the colour,oxidative and microbiological stability of packed beef

The objective of this study was to evaluate the influence of two different vacuum ageing times (7 and 14 days) and the impact of the modified atmosphere packaging (MAP) configuration (gas/product ratios: 0.5 and 1 and gas composition: 70% O₂ + 30% CO₂ and 40% O₂ + 30% CO₂ + 30% N₂) on the quality of fresh beef during subsequent storage at 4 °C. For this purpose, three separate experiments were performed. For each experiment, two different muscles (Longissimus dorsi and Biceps femoris) were sampled from four double‐muscled Belgian Blue beef carcasses. Next to colour, also the evolution in microbial load, pH, O₂ and CO₂ in the headspace and lipid oxidation at the meat surface were evaluated. A vacuum ageing for 14 days compared with 7 days resulted in a higher initial microbial load on the day of MAP packaging, which resulted finally in a significantly shorter shelf life. This ageing effect was less pronounced on the colour stability and lipid oxidation of the meat samples. No significant influence of the packaging configuration on any of the analysed parameters (colour, microbial load, pH and lipid oxidation at the meat surface) was observed.