Enhanced Activity and Sustained Release of Protocatechuic Acid,a Natural Antibacterial Agent,from Hybrid Nanoformulations with Zinc Oxide Nanoparticles

Hybrid nanostructures can be developed with inorganic nanoparticles (NPs) such as zinc oxide (ZnO) and natural antibacterials. ZnO NPs can also exert antibacterial effects, and we used them here to examine their dual action in combination with a natural antibacterial agent, protocatechuic acid (PCA). To produce hybrid nanoformulations, we functionalized ZnO NPs with four types of silane organic molecules and successfully linked them to PCA. Physicochemical assessment confirmed PCA content up to ~18% in hybrid nanoformulations, with a PCA entrapment efficiency of ~72%, indicating successful connection. We then investigated the in vitro release kinetics and antibacterial effects of the hybrid against Staphylococcus aureus. PCA release from hybrid nanoformulations varied with silane surface modification. Within 98 h, only 8% of the total encapsulated PCA was released, suggesting sustained long-term release. We used nanoformulation solutions collected at days 3, 5, and 7 by disc diffusion or log reduction to evaluate their antibacterial effect against S. aureus. The hybrid nanoformulation showed efficient antibacterial and bactericidal effects that also depended on the surface modification and at a lower minimum inhibition concentration compared with the separate components. A hybrid nanoformulation of the PCA prodrug and ZnO NPs offers effective sustained-release inhibition of S. aureus growth.     

Mode of Action of 1-Naphthylphthalamic Acid in Conspicuous Local Stem Swelling of Succulent Plant,Bryophyllum calycinum: Relevance to the Aspects of Its Histological Observation and Comprehensive Analyses of Plant Hormones

The mode of action of 1-naphthylphthalamic acid (NPA) to induce conspicuous local stem swelling in the area of its application to the growing internode in intact Bryophyllum calycinum was studied based on the aspects of histological observation and comprehensive analyses of plant hormones. Histological analyses revealed that NPA induced an increase in cell size and numerous cell divisions in the cortex and pith, respectively, compared to untreated stem. In the area of NPA application, vascular tissues had significantly wider cambial zones consisting of 5–6 cell layers, whereas phloem and xylem seemed not to be affected. This indicates that stem swelling in the area of NPA application is caused by stimulation of cell division and cell enlargement mainly in the cambial zone, cortex, and pith. Comprehensive analyses of plant hormones revealed that NPA substantially increased endogenous levels of indole-3-acetic acid (IAA) in the swelling area. NPA also increased endogenous levels of cytokinins, jasmonic acid, and its precursor, 12-oxo-phytodienoic acid, but did not increase abscisic acid and gibberellin levels. It was shown, using radiolabeled ¹⁴C-IAA, that NPA applied to the middle of internode segments had little effect on polar auxin transport, while 2,3,5-triiodobenzoic acid substantially inhibited it. These results strongly suggest that NPA induces changes in endogenous levels of plant hormones, such as IAA, cytokinins, and jasmonic acid, and their hormonal crosstalk results in a conspicuous local stem swelling. The possible different mode of action of NPA from other polar auxin transport inhibitors in succulent plants is extensively discussed.     

LATS1 Is a Mediator of Melanogenesis in Response to Oxidative Stress and Regulator of Melanoma Growth

The LATS1 kinase has been described as a tumor suppressor in various cancers. However, its role in melanoma has not been fully elucidated. There are several processes involved in tumorigenesis, including melanin production. Melanin content positively correlates with the level of reactive oxygen species (ROS) inside the cell. Accordingly, the purpose of the study was to assess the role of LATS1 in melanogenesis and oxidative stress and its influence on tumor growth. We have knocked down LATS1 in primary melanocytes and melanoma cells and found that its expression is crucial for melanin synthesis, ROS production, and oxidative stress response. We showed that LATS1 ablation significantly decreased the melanogenesis markers’ expression and melanin synthesis in melanocyte and melanoma cell lines. Moreover, silencing LATS1 resulted in enhanced oxidative stress. Reduced melanin content in LATS1 knocked down tumors was associated with increased tumor growth, pointing to melanin’s protective role in this process. The study demonstrated that LATS1 is highly engaged in melanogenesis and oxidative stress control and affects melanoma growth. Our results may find the implications in the diagnosis and treatment of pigmentation disorders, including melanoma.     

Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy—Part II. Toxicity,Pharmacokinetics and Biodistribution

Metastatic castration-resistant prostate cancer (mCRPC) is a progressive and incurable disease with poor prognosis for patients. Despite introduction of novel therapies, the mortality rate remains high. An attractive alternative for extension of the life of mCRPC patients is PSMA-based targeted radioimmunotherapy. In this paper, we extended our in vitro study of ²²³Ra-labeled and PSMA-targeted NaA nanozeolites [²²³RaA-silane-PEG-D2B] by undertaking comprehensive preclinical in vitro and in vivo research. The toxicity of the new compound was evaluated in LNCaP C4-2, DU-145, RWPE-1 and HPrEC prostate cells and in BALB/c mice. The tissue distribution of ¹³³Ba- and ²²³Ra-labeled conjugates was studied at different time points after injection in BALB/c and LNCaP C4-2 tumor-bearing BALB/c Nude mice. No obvious symptoms of antibody-free and antibody-functionalized nanocarriers cytotoxicity and immunotoxicity was found, while exposure to ²²³Ra-labeled conjugates resulted in bone marrow fibrosis, decreased the number of WBC and platelets and elevated serum concentrations of ALT and AST enzymes. Biodistribution studies revealed high accumulation of ²²³Ra-labeled conjugates in the liver, lungs, spleen and bone tissue. Nontargeted and PSMA-targeted radioconjugates exhibited a similar, marginal uptake in tumour lesions. In conclusion, despite the fact that NaA nanozeolites are safe carriers, the intravenous administration of NaA nanozeolite-based radioconjugates is dubious due to its high accumulation in the lungs, liver, spleen and bones.     

The Influence of an Adrenergic Antagonist Guanethidine on the Distribution Pattern and Chemical Coding of Caudal Mesenteric Ganglion Perikarya and Their Axons Supplying the Porcine Bladder

This study was aimed at disclosing the influence of intravesically instilled guanethidine (GUA) on the distribution, relative frequency and chemical coding of both the urinary bladder intramural sympathetic nerve fibers and their parent cell bodies in the caudal mesenteric ganglion (CaMG) in juvenile female pigs. GUA instillation led to a profound decrease in the number of perivascular nerve terminals. Furthermore, the chemical profile of the perivascular innervation within the treated bladder also distinctly changed, as most of axons became somatostatin-immunoreactive (SOM-IR), while in the control animals they were found to be neuropeptide Y (NPY)-positive. Intravesical treatment with GUA led not only to a significant decrease in the number of bladder-projecting tyrosine hydroxylase (TH) CaMG somata (94.3 ± 1.8% vs. 73.3 ± 1.4%; control vs. GUA-treated pigs), but simultaneously resulted in the rearrangement of their co-transmitters repertoire, causing a distinct decrease in the number of TH⁺/NPY⁺ (89.6 ± 0.7% vs. 27.8 ± 0.9%) cell bodies and an increase in the number of SOM-(3.6 ± 0.4% vs. 68.7 ± 1.9%), calbindin-(CB; 2.06 ± 0.2% vs. 9.1 ± 1.2%) or galanin-containing (GAL; 1.6 ± 0.3% vs. 28.2 ± 1.3%) somata. The present study provides evidence that GUA significantly modifies the sympathetic innervation of the porcine urinary bladder wall, and thus may be considered a potential tool for studying the plasticity of this subdivision of the bladder innervation.     

Some Dietary Phenolic Compounds Can Activate Thyroid Peroxidase and Inhibit Lipoxygenase-Preliminary Study in the Model Systems

The presented research concerns the triple activity of trans-cinnamic (tCA), ferulic (FA) and syringic acids (SA). They act as thyroid peroxidase (TPO) activators, lipoxygenase (LOX) inhibitors and show antiradical activity. All compounds showed a dose-dependent TPO activatory effect, thus the AC₅₀ value (the concentration resulting in 50% activation) was determined. The tested compounds can be ranked as follows: tCA > FA > SA with AC₅₀ = 0.10, 0.39, 0.69 mM, respectively. Strong synergism was found between FA and SA. The activatory effects of all tested compounds may result from interaction with the TPO allosteric site. It was proposed that conformational change resulting from activator binding to TPO allosteric pocket results from the flexibility of a nearby loop formed by residues Val352-Tyr363. All compounds act as uncompetitive LOX inhibitors. The most effective were tCA and SA, whereas the weakest was FA (IC₅₀ = 0.009 mM and IC₅₀ 0.027 mM, respectively). In all cases, an interaction between the inhibitors carboxylic groups and side-chain atoms of Arg102 and Arg139 in an allosteric pocket of LOX was suggested. FA/tCA and FA/SA acted synergistically, whereas tCA/SA demonstrated antagonism. The highest antiradical activity was found in the case of SA (IC₅₀ = 0.22 mM). FA/tCA and tCA/SA acted synergistically, whereas antagonism was found for the SA/FA mixture.     

Antifungal resistance and physicochemical attributes of apricots coated with potassium sorbate‐added carboxymethyl cellulose‐based emulsion

Antifungal effectiveness of potassium sorbate (KS) incorporated into edible coating composed of carboxymethyl cellulose and candelilla wax blend (CMC‐CnW) was tested on apricots inoculated with fungi. The efficiency of KS‐added coating was higher than KS‐free formulation. The antifungal action of KS‐free coating was likely associated with a reduced access of oxygen to the infection sites and, consequently, modification of the gaseous atmosphere within the fruit tissues. Rhizopus nigricans as the fastest growing fungus was the most resistant to the coating treatment. In turn, KS‐loaded coating was very effective against Botrytis cinerea and Monilinia fructigena. Coating significantly delayed softening of apricots. The results of this study demonstrate that KS can be incorporated into coating to control common fungal diseases of apricots. Nevertheless, the CMC‐CnW coating treatment inhibited the respiratory functions and caused deterioration in the fruit sensory quality.     

Reasons for the lack of chemical stability of treated water rich in magnesium

Chemical stability of water should be high enough to ensure that the water reaching the consumers would have the same composition as at the treatment plant. The drinking water supplied by one of the water treatment plants for the city of Poznań was observed to produce periodically white non-sedimenting precipitate on boiling, deteriorating its organoleptic properties. The phenomenon was found to be related to a high content of magnesium in the water taken for treatment and low content of other ions besides bicarbonates. XRD and SEM analyses have shown that a low ratio of calcium ions to magnesium ions leads to formation of calcite crystals on water boiling in which a fraction of cationic crystallographic sites are substituted with Mg²⁺ ions giving (Ca_1−xMg_x)CO₃ crystallites. Such crystallites have smaller size than those of calcite formed on boiling water coming from other Poznań suppliers. The smaller size of the crystallites is responsible for their slower sedimentation and hence the observed increase in the water turbidity on its boiling. It has been proved that the appearance of precipitates in drinking water at the consumers can be achieved by reduction of the Mg/(Mg + Ca) ratio to below 3, which would inhibit peptisation of the precipitate and prevent water opacity and/or adjustment of pH of the raw water and removal of the carbon dioxide released to convert some carbonate hardness into non-carbonate one. These measures will limit the amount of the precipitate forming upon water boiling and change its microcrystalline type into an easier sedimenting one.     

Digestion and bioavailability of bioactive phytochemicals

There are many scientific reports on determination of the content and biological activity of compounds found in food. However, these analyses are not sufficient to determine their effect on the human body. During digestion of food ingredients, many changes can modify their structure and this may affect their absorption and bioactivity. Many phenolic aglycones are hydrophilic and can be absorbed through biological membranes by diffusion. However, most polyphenols occur in the glycosidic form, which undoubtedly affects their absorption in the intestine. Oligopeptides are also absorbable via secondary active transport but based on the hydrogen ion gradient or with transporter PepT1. The bioavailability of phytochemicals is determined by their molecular weight or chemical structure and the food matrix. Accordingly, the aim of this work was to present the novel scientific reports related to the influence the many factors on digestibility, bioaccessibility and activity of selected bioactive compounds of plant origin.