Functionalised Anodised Aluminium Oxide as a Biocidal Agent

In this article, we describe the antimicrobial properties of a new composite based on anodic aluminium oxide (AAO) membranes containing propyl-copper-phosphonate units arranged at a predetermined density inside the AAO channels. The samples were prepared with four concentrations of copper ions and tested as antimicrobial drug on four different strains of Escherichia coli (K12, R2, R3 and R4). For comparison, the same strains were tested with three types of antibiotics using the minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests. Moreover, DNA was isolated from the analysed bacteria which was additionally digested with formamidopyrimidine-DNA glycosylase (Fpg) protein from the group of repair glycosases. These enzymes are markers of modified oxidised bases in nucleic acids produced during oxidative stress in cells. Preliminary cellular studies, MIC and MBC tests and digestion with Fpg protein after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than antibiotics such as ciprofloxacin, bleomycin and cloxacillin. The described composites are highly specific for the analysed model Escherichia coli strains and may be used in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the progressing pandemic era. The results show much stronger antibacterial properties of the functionalised membranes on the action of bacterial membranes in comparison to the antibiotics in the Fpg digestion experiment. This is most likely due to the strong induction of oxidative stress in the cell through the breakdown of the analysed bacterial DNA. We have also observed that the intermolecular distances between the functional units play an important role for the antimicrobial properties of the used material. Hence, we utilised the idea of the 2D solvent to tailor them.     

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.     

I2-Imidazoline Ligand CR4056 Improves Memory,Increases ApoE Expression and Reduces BBB Leakage in 5xFAD Mice

Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer’s disease (AD). We recently demonstrated that the I2-ligand BU224 reversed memory impairments in AD transgenic mice and this effect was not because of reductions in amyloid-β (Aβ) deposition. In this study, our aim was to determine the therapeutic potential of the powerful analgesic I2-imidazoline ligand CR4056 in the 5xFAD model of AD, since this ligand has been proven to be safely tolerated in humans. Sub-chronic oral administration of CR4056 (30 mg/kg for 10 days) led to an improvement in recognition memory in 6-month-old 5xFAD mice, but not in wild-type littermates, without affecting Aβ levels or deposition. Our results also revealed a change in the profile of microglia by CR4056, resulting in a suppression of pro-inflammatory activated microglia, but increased the density of astrocytes and the expression of ApoE, which is mainly produced by these glial cells. In addition, CR4056 restored fibrinogen extravasation, affecting the distribution of markers of astrocytic end feet in blood vessels. Therefore, these results suggest that CR4056 protects against Aβ-mediated neuroinflammation and vascular damage, and offers therapeutic potential at any stage of AD.     

Melatonin and the Brain–Heart Crosstalk in Neurocritically Ill Patients—From Molecular Action to Clinical Practice

Brain injury, especially traumatic brain injury (TBI), may induce severe dysfunction of extracerebral organs. Cardiac dysfunction associated with TBI is common and well known as the brain–heart crosstalk, which broadly refers to different cardiac disorders such as cardiac arrhythmias, ischemia, hemodynamic insufficiency, and sudden cardiac death, which corresponds to acute disorders of brain function. TBI-related cardiac dysfunction can both worsen the brain damage and increase the risk of death. TBI-related cardiac disorders have been mainly treated symptomatically. However, the analysis of pathomechanisms of TBI-related cardiac dysfunction has highlighted an important role of melatonin in the prevention and treatment of such disorders. Melatonin is a neurohormone released by the pineal gland. It plays a crucial role in the coordination of the circadian rhythm. Additionally, melatonin possesses strong anti-inflammatory, antioxidative, and antiapoptotic properties and can modulate sympathetic and parasympathetic activities. Melatonin has a protective effect not only on the brain, by attenuating its injury, but on extracranial organs, including the heart. The aim of this study was to analyze the molecular activity of melatonin in terms of TBI-related cardiac disorders. Our article describes the benefits resulting from using melatonin as an adjuvant in protection and treatment of brain injury-induced cardiac dysfunction.     

Synthesis,In Vitro,and Computational Studies of PTP1B Phosphatase Inhibitors Based on Oxovanadium(IV) and Dioxovanadium(V) Complexes

One of the main goals of recent bioinorganic chemistry studies has been to design and synthesize novel substances to treat human diseases. The promising compounds are metal-based and metal ion binding components such as vanadium-based compounds. The potential anticancer action of vanadium-based compounds is one of area of investigation in this field. In this study, we present five oxovanadium(IV) and dioxovanadium(V) complexes as potential PTP1B inhibitors with anticancer activity against the MCF-7 breast cancer cell line, the triple negative MDA-MB-231 breast cancer cell line, and the human keratinocyte HaCaT cell line. We observed that all tested compounds were effective inhibitors of PTP1B, which correlates with anticancer activity. [VO(dipic)(dmbipy)]·2 H₂O (Compound 4) and [VOO(dipic)](2-phepyH)·H₂O (Compound 5) possessed the greatest inhibitory effect, with IC₅₀ 185.4 ± 9.8 and 167.2 ± 8.0 nM, respectively. To obtain a better understanding of the relationship between the structure of the examined compounds and their activity, we performed a computer simulation of their binding inside the active site of PTP1B. We observed a stronger binding of complexes containing dipicolinic acid with PTP1B. Based on our simulations, we suggested that the studied complexes exert their activity by stabilizing the WPD-loop in an open position and limiting access to the P-loop.     

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.     

Reorganization of the Brain Extracellular Matrix in Hippocampal Sclerosis

The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE in correlation to clinical findings. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic episodes had a less intense diffuse WFA staining in Cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein, and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons’ excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy.     

Effects of Probiotic Supplementation during Pregnancy on the Future Maternal Risk of Metabolic Syndrome

Probiotics are live microorganisms that induce health benefits in the host. Taking probiotics is generally safe and well tolerated by pregnant women and their children. Consumption of probiotics can result in both prophylactic and therapeutic effects. In healthy adult humans, the gut microbiome is stable at the level of the dominant taxa: Bacteroidetes, Firmicutes and Actinobacteria, and has a higher presence of Verrucomicrobia. During pregnancy, an increase in the number of Proteobacteria and Actinobacteria phyla and a decrease in the beneficial species Roseburia intestinalis and Faecalibacterium prausnitzii are observed. Pregnancy is a “window” to the mother’s future health. The aim of this paper is to review studies assessing the potentially beneficial effects of probiotics in preventing the development of diseases that appear during pregnancy, which are currently considered as risk factors for the development of metabolic syndrome, and consequently, reducing the risk of developing maternal metabolic syndrome in the future. The use of probiotics in gestational diabetes mellitus, preeclampsia and excessive gestational weight gain is reviewed. Probiotics are a relatively new intervention that can prevent the development of these disorders during pregnancy, and thus, would reduce the risk of metabolic syndrome resulting from these disorders in the mother’s future.     

The Potential Application of Starch and Walnut Shells as Biofillers for Natural Rubber (NR) Composites

The goal of this study was application of corn starch and ground walnut shells in various amounts by weight as biofillers of natural rubber (NR) biocomposites. Additionally, ionic liquid 1-butyl-3-methylimidazolium chloride (BmiCl) and (3-aminopropyl)-triethoxysilane (APTES) were used to increase the activity of biofillers and to improve the curing characteristics of NR composites. The effect of biofillers used and their modification with aminosilane or ionic liquid on the curing characteristics of NR composites and their functional properties, including crosslink density, mechanical properties in static and dynamic conditions, hardness, thermal stability and resistance to thermo-oxidative aging were investigated. Starch and ground walnut shells were classified as inactive fillers, which can be used alternatively to commercial inactive fillers, e.g., chalk. BmiCl and APTES were successfully used to support the vulcanization and to improve the dispersion of biofillers in NR elastomer matrix. Vulcanizates with starch, especially those containing APTES and BmiCl, exhibited improved tensile properties due to the higher crosslink density and homogenous dispersion of starch, which resulted from BmiCl addition. NR filled with ground walnut shells demonstrated improved resistance to thermo-oxidative aging. It resulted from lignin present in walnut shells, the components of which belong to polyphenols, that have an antioxidant activity.