Gold (III) Derivatives in Colon Cancer Treatment

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.     

Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis.     

The Composites of PCL and Tetranuclear Titanium(IV)-oxo Complexes as Materials Exhibiting the Photocatalytic and the Antimicrobial Activity

Excessive misuse of antibiotics and antimicrobials has led to a spread of microorganisms resistant to most currently used agents. The resulting global threats has driven the search for new materials with optimal antimicrobial activity and their application in various areas of our lives. In our research, we focused on the formation of composite materials produced by the dispersion of titanium(IV)-oxo complexes (TOCs) in poly(ε-caprolactone) (PCL) matrix, which exhibit optimal antimicrobial activity. TOCs, of the general formula [Ti₄O₂(OⁱBu)₁₀(O₂CR’)₂] (R’ = PhNH₂ (1), C₁₃H₉ (2)) were synthesized as a result of the direct reaction of titanium(IV) isobutoxide and 4-aminobenzoic acid or 9-fluorenecarboxylic acid. The microcrystalline powders of (1) and (2), whose structures were confirmed by infrared (IR) and Raman spectroscopy, were dispersed in PCL matrixes. In this way, the composites PCL + nTOCs (n = 5 and 20 wt.%) were produced. The structure and physicochemical properties were determined on the basis of Raman microscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), electron paramagnetic resonance spectroscopy (EPR), and UV–Vis diffuse reflectance spectroscopy (DRS). The degree of TOCs distribution in the polymer matrix was monitored by scanning electron microscopy (SEM). The addition of TOCs micro grains into the PCL matrix only slightly changed the thermal and mechanical properties of the composite compared to the pure PCL. Among the investigated PCL + TOCs systems, promising antibacterial properties were confirmed for samples of PCL + n(2) (n = 5, 20 wt.%) composites, which simultaneously revealed the best photocatalytic activity in the visible range.     

Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics

Three aromatic heptaene macrolide antifungal antibiotics, Candicidin D, Partricin A (Gedamycin) and Partricin B (Vacidin) were subjected to controlled cis-trans → all trans photochemical isomerization. The obtained all-trans isomers demonstrated substantially improved in vitro selective toxicity in the Candida albicans cells: human erythrocytes model. This effect was mainly due to the diminished hemotoxicity. The molecular modeling studies on interactions between original antibiotics and their photoisomers with ergosterol and cholesterol revealed some difference in free energy profiles of formation of binary antibiotic/sterol complexes in respective membrane environments. Moreover, different geometries of heptaene: sterol complexes and variations in polyene macrolide molecule alignment in cholesterol-and ergosterol-containing membranes were found. None of these effects are of the crucial importance for the observed improvement of selective toxicity of aromatic heptaene antifungals but each seems to provide a partial contribution.     

On the fine emulsion polymerization of styrene with non-ionic emulsifier

Summary The fine emulsion polymerizations of styrene initiated by a redox system ammonium peroxodisulfate/sodium thiosulfite stabilized by a non-ionic emulsifier were kinetically investigated. The dependence of the rate of polymerization on conversion or the emulsifier concentration was described by a curve with maximum at medium conversion. The maximum rate of polymerization is proportional to the − 0.45^th and 1.5^th power of initiator and emulsifier concentration, the number of particles to the 0.32^nd and 1.3^rd power of initiator and emulsifier concentration and the molecular weight to the − 0.62^th and −0.97^th power of initiator and emulsifier concentration, respectively. The results show a strong decrease in turbidity at around 20% conversion when emulsion turns into translucent latex. Deviation from the micellar nucleation model was attributed to the solubility of emulsifier in monomer, high level of nonmicellar aggregates, thick interfacial layer and transfer emulsion to microemulsion. The strong decrease of molecular weight with increasing emulsifier concentration is attributed to chain transfer events promoted by the high level of emulsifier at the reaction loci. Received: 16 November 1998/Revised version: 25 May, 10 October 1999/Accepted: 10 October 1999     

Electrochemical micromachining of a Zr-based bulk metallic glass using a micro-tool electrode technique

For the first time the possibility of electrochemical micromachining (ECMM) of a Zr-based bulk metallic glass (BMG) using a micro-tool electrode technique is reported. It is demonstrated that the choice of the electrolyte chemistry is substantial for a successful ECMM processing. For the bulk glassy Zr₅₉Ti₃Cu₂₀Al₁₀Ni₈ alloy a concentrated aqueous NaNO₃ standard machining solution is not suitable due to formation of thick and dense corrosion product layers which hinder the machining of structures with high aspect ratio. On the other hand, a commercial methanolic HClO₄ solution is shown to be very promising. In the first experiments with this electrolyte micro-hole structures were machined with aspect ratios of about 1 at depths of ～40 μm. The effect of process parameters such as pulse voltage and pulse length was investigated and their influence on the machined structure morphology is established. In a first approach the potential and challenges of this electrochemical micromachining technique for microforming of multi-component bulk metallic glass surfaces will be discussed.     

Development of a realistic human respiratory tract cast representing physiological thermal conditions

Toxicological assessment of inhaled aerosols and their effects on respiratory tissue cells requires accurate measurements of particle delivery, properties, evolution, and deposition in the human respiratory tract. These measurements are affected by both anatomical features and physiological factors, such as thermal conditions in the respiratory system. We constructed a segmented cast model, based on a realistic geometry of the human respiratory tract, equipped with features to control the temperature of the air flow. We then evaluated the thermal equilibrium of the air flow through the cast using both experimental measurements and computational fluid dynamics modeling. Uniform temperature distribution in the cast shell was achieved using parallel connection of the cast segments to a thermal bath by flow splitter. Air temperature inside the cast was shown to require <1?min to equilibrate with the temperature of the cast during internal circulation of hot water. Air flow temperature was shown to equilibrate with the cast temperature in the mouth–throat region, and a uniform temperature distribution was achieved in the other segments, resembling the thermal conditions of respiratory flow in the human lung. We showed that the cast successfully represents the physiological thermal conditions of the human respiratory system.     

Subtyping botulinum neurotoxins by sequential multiple endoproteases in-gel digestion coupled with mass spectrometry

Botulinum neurotoxin (BoNT) is one of the most toxic substances known. BoNT is classified into seven distinct serotypes labeled A-G. Among individual serotypes, researchers have identified subtypes based on amino acid variability within a serotype and toxin variants with minor amino acid sequence differences within a subtype. BoNT subtype identification is valuable for tracing and tracking bacterial pathogens. A proteomics approach is useful for BoNT subtyping since botulism is caused by botulinum neurotoxin and does not require the presence of the bacteria or its DNA. Enzymatic digestion and peptide identification using tandem mass spectrometry determines toxin protein sequences. However, with the conventional one-step digestion method, producing sufficient numbers of detectable peptides to cover the entire protein sequence is difficult, and incomplete sequence coverage results in uncertainty in distinguishing BoNT subtypes and toxin variants because of high sequence similarity. We report here a method of multiple enzymes and sequential in-gel digestion (MESID) to characterize the BoNT protein sequence. Complementary peptide detection from toxin digestions has yielded near-complete sequence coverage for all seven BoNT serotypes. Application of the method to a BoNT-contaminated carrot juice sample resulted in the identification of 98.4% protein sequence which led to a confident determination of the toxin subtype.     

Nanofibers prepared by needleless electrospinning technology as scaffolds for wound healing

Electrospun gelatin and poly-ε-caprolactone (PCL) nanofibers were prepared using needleless technology and their biocompatibility and therapeutic efficacy have been characterized in vitro in cell cultures and in an experimental model of a skin wound. Human dermal fibroblasts, keratinocytes and mesenchymal stem cells seeded on the nanofibers revealed that both nanofibers promoted cell adhesion and proliferation. The effect of nanofibers on wound healing was examined using a full thickness wound model in rats and compared with a standard control treatment with gauze. Significantly faster wound closure was found with gelatin after 5 and 10 days of treatment, but no enhancement with PCL nanofibers was observed. Histological analysis revealed enhanced epithelialisation, increased depth of granulation tissue and increased density of myofibroblasts in the wound area with gelatin nanofibers. The results show that gelatin nanofibers produced by needleless technology accelerate wound healing and may be suitable as a scaffold for cell transfer and skin regeneration.     

The Simple Method of Preparation of Highly Carboxylated Bacterial Cellulose with Ni- and Mg-Ferrite-Based Versatile Magnetic Carrier for Enzyme Immobilization

The bacterial cellulose (BC) is a versatile biopolymer of microbial origin characterized by high purity and unusual water and material properties. However, the native BC contains a low number of functional groups, which significantly limits its further application. The main goal of its effective modification is to use methods that allow the unusual properties of BC to be retained and the desired functional group to be efficiently introduced. In the present study, the new magnetic carrier based on functionalized citric acid (CA) bacterial cellulose was developed and tested to support critical industrial enzymes such as lipase B from Candida antarctica and phospholipase A from Aspergillus oryzae. The applied method allowed BC to be effectively modified by citric acid and a sufficient number of carboxylic groups to be introduced, up to 3.6 mmol of COOH per gram of dry mass of the prepared carrier. The DSC and TGA analyses revealed carrier stability at operational temperatures in the range of 20 °C to 100 °C and substantially influenced the amount of the introduced carboxyl groups on carrier properties. Both enzymes’ immobilization significantly improves their thermal stability at 60 °C without a significant thermal and pH optima effect. The analyzed enzymes showed good operational stability with a significant residual activity after ten cycles of repeated uses. The new magnetic carrier based on highly carboxylated bacterial cellulose has a high application capability as matrix for immobilization the various enzymes of industrial interest.