Effect of Thermal Treatment on the Photocatalytic Activity in Visible Light of TiO<Subscript>2</Subscript>-W Flame Spray Synthesised Nanopowders

Effect of W doping as well as a thermal treatment on the structural and photocatalytic properties of TiO₂ produced by flame spray synthesis (FSS) were the subject of investigation. Structural properties were studied by means of X-ray diffraction (XRD), BET adsorption isotherm and transmission electron microscopy (TEM). The surface condition was investigated by X-ray photoelectron spectroscopy (XPS) and differential scanning calorimetry (DSC) and differential thermal and thermogravimetric analysis (DTA-TGA). The photocatalytic properties were studied by optical measurements and photodecomposition of methylene blue under visible irradiation. It was found that the photoactivity in the visible region was enhanced significantly by the W-doping as well as by additional thermal treatment of those nanopowders. The obtained TiO₂-W nanopowders exhibited higher performance under visible light than P25.     

A Photoexcited Porphyrin System as a Biomimetic Catalyst for D-limonene Biotransformation

A photoexcited porphyrin system has been found to be an efficient catalyst for D-limonene biotransformation. The catalyst showed high selectivity in hydroxylation of D-limonene. The best catalyst for limonene biotransformation was 5,10,15,20-Tetraphenylporphyrin (H₂TPP), which gave the highest accumulation of carvone and an unknown product with a verbenone-like mass spectrum. The highest conversion yield of these products was favoured at 1:2 molar ratio of H₂TPP to limonene. Some factors affecting the biotransformation yield were also investigated. Maximal yield of carvone was obtained in the medium containing 90% of the substrate, within the period of 18–36 h. Mechanism involved in limonene biotransformation catalysed by H₂TPP is also discussed.     

Bimetallic Au–Cu, Ag–Cu/CrAl3O6 Catalysts for Methanol Synthesis

The influence of silver and gold addition on the activity and physicochemical properties of supported Cu/CrAl₃O₆ catalysts was the aim of this work. The reduction of CrAl₃O₆ support shows only one reduction stage attributed to Cr (VI) species reduction originating from previously oxidized binary oxide. Supported copper catalysts reduce in one or two stages depending on copper concentration representing the reduction of copper oxide—CuO, copper oxide chemically combined with Cr(III) oxide as copper chromite—CuCr₂O₄ and Cr(VI) species originating from surface chromate ions CrO₄ ^2?. Additionally, the introduction of silver into supported copper catalysts Cu/CrAl₃O₆ can led to the appearance of silver chromate phase. XRD investigations of support CrAl₃O₆ alone, supported copper and gold and silver promoted copper supported catalysts calcined at 400, 700 and 900 °C indicated the presence of highly amorphous alumina γ-Al₂O₃ like structure network in which some of cationic locations of aluminum were occupied by chromium atoms and small quantities of α-Cr₂O₃ phase. Additionally, for copper, silver–copper, and gold–copper supported catalysts the following oxide phases were distinguished: monometallic oxides CuO, Ag₂O, binary oxides CuAl₂O₄, Ag₂CrO₄, CuCr₂O₄ and even ternary oxide CuAlCrO₄. In the case of gold promoted copper supported catalysts metallic gold phase was detected. Activity tests carried out for these catalysts show that the most active was 20 wt.% Cu/CrAl₃O₆ catalyst. Promotion of copper catalysts by silver improves the activity in methanol synthesis, what can be assigned to silver chromate formation. The analogical gold chromate like formation was not confirmed.     

Enhancement of bio-electrocatalytic oxygen reduction at the composite film of cobalt porphyrin immobilized within the carbon nanotube-supported peroxidase enzyme

Combination of multi-walled carbon nanotubes, cobalt porphyrin, and peroxidase (horseradish, cabbage) enzyme in the film (deposited onto glassy carbon electrode substrate) produces a bio-electrocatalytic system capable of effective reduction of oxygen in such neutral media as 0.1 mol dm⁻³ KCl and 0.1 mol dm⁻³ KCl + 0.01 citrate buffer (pH 6).Carbon nanotubes have been modified with ultra-thin layers of 4-(pyrrole-1-yl) benzoic acid, or phosphododecamolybdate, to form stable colloidal suspensions of carbon nanostructures. The resulting inks have been utilized during sequential deposition of components. Co-existence of cobalt porphyrin, peroxidase enzyme together with dispersed carbon nanotubes leads to synergistic effect that is evident from some positive shift of the oxygen reduction voltammetric potentials (more than 50 mV in citrate buffer) and significant (ca. twice) increase of voltammetric currents (relative to those of the enzyme-free system). The multi-component bio-electrocatalytic film has also exhibited relatively higher activity towards reduction of hydrogen peroxide. It is reasonable to expect that the reduction of oxygen is initiated at cobalt porphyrin redox centers, and the undesirable hydrogen peroxide intermediate is further reduced at the horseradish or cabbage peroxidase enzymatic sites. An important function of carbon nanotubes is to improve transport of electrons within the bio-electrocatalytic multi-component film.     

The Involvement of Xanthone and (E)-Cinnamoyl Chromophores for the Design and Synthesis of Novel Sunscreening Agents

Excessive UV exposure contributes to several pathological conditions like skin burns, erythema, premature skin aging, photodermatoses, immunosuppression, and skin carcinogenesis. Effective protection from UV radiation may be achieved with the use of sunscreens containing UV filters. Currently used UV filters are characterized by some limitations including systemic absorption, endocrine disruption, skin allergy induction, and cytotoxicity. In the research centers all over the world new molecules are developed to improve the safety, photostability, solubility, and absorption profile of new derivatives. In our study, we designed and synthesized seventeen novel molecules by combining in the structures two chromophores: xanthone and (E)-cinnamoyl moiety. The ultraviolet spectroscopic properties of the tested compounds were confirmed in chloroform solutions. They acted as UVB or UVA/UVB absorbers. The most promising compound 9 (6-methoxy-9-oxo-9H-xanthen-2-yl)methyl (E)-3-(2,4-dimethoxyphenyl)acrylate) absorbed UV radiation in the range 290–369 nm. Its photoprotective activity and functional photostability were further evaluated after wet milling and incorporation in the cream base. This tested formulation with compound 9 possessed very beneficial UV protection parameters (SPF_{in vitro} of 19.69 ± 0.46 and UVA PF of 12.64 ± 0.32) which were similar as broad-spectrum UV filter tris-biphenyl triazine. Additionally, compound 9 was characterized by high values of critical wavelength (381 nm) and UVA/UVB ratio (0.830) thus it was a good candidate for broad-spectrum UV filter and it might protect skin against UVA-induced photoaging. Compound 9 were also shown to be photostable, non-cytotoxic at concentrations up to 50 µM when tested on five cell lines, and non-mutagenic in Ames test. It also possessed no estrogenic activity, according to the results of MCF-7 breast cancer model. Additionally, its favorable lipophilicity (miLogP = 5.62) does not predispose it to penetrate across the skin after topical application.     

Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma

Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPK, AKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, the cancer progresses. These activating gene mutations for the EGFR are present in 10–20% of lung adenocarcinomas. Approximately 3–7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway, stimulates the proliferation of tumor cells, and inhibits apoptosis. A new group of drugs—small-molecule tyrosine kinase inhibitors—has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases.     

Sirtuins as Important Factors in Pathological States and the Role of Their Molecular Activity Modulators

Sirtuins (SIRTs), enzymes from the family of NAD⁺-dependent histone deacetylases, play an important role in the functioning of the body at the cellular level and participate in many biochemical processes. The multi-directionality of SIRTs encourages scientists to undertake research aimed at understanding the mechanisms of their action and the influence that SIRTs have on the organism. At the same time, new substances are constantly being sought that can modulate the action of SIRTs. Extensive research on the expression of SIRTs in various pathological conditions suggests that regulation of their activity may have positive results in supporting the treatment of certain metabolic, neurodegenerative or cancer diseases or this connected with oxidative stress. Due to such a wide spectrum of activity, SIRTs may also be a prognostic markers of selected pathological conditions and prove helpful in assessing their progression, especially by modulating their activity. The article presents and discusses the activating or inhibiting impact of individual SIRTs modulators. The review also gathered selected currently available information on the expression of SIRTs in individual disease cases as well as the biological role that SIRTs play in the human organism, also in connection with oxidative stress condition, taking into account the progress of knowledge about SIRTs over the years, with particular reference to the latest research results.     

Role of HMOX1 Promoter Genetic Variants in Chemoresistance and Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia

Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 gene (HMOX1) expression is modulated by two polymorphisms in the promoter region: (GT)n-length polymorphism and single-nucleotide polymorphism (SNP) A(−413)T, with short GT repeat sequences and 413-A variants linked to an increased HO-1 inducibility. We found that the short alleles are significantly more frequent in ALL patients in comparison to the control group, and that their presence may be associated with a higher risk of treatment failure, reflecting the role of HO-1 in chemoresistance. We also observed that the presence of short alleles may predispose to develop chemotherapy-induced neutropenia. In case of SNP, the 413-T variant co-segregated with short or long alleles, while 413-A almost selectively co-segregated with long alleles, hence it is not possible to determine if SNPs are actually of phenotypic significance. Our results suggest that HO-1 can be a potential target to overcome the treatment failure in ALL patients.     

The Peculiar Structure of Acetobacter pasteurianus CIP103108 LPS Core Oligosaccharide

Acetobacter pasteurianus, a member of the Alphaproteobacteria, is an acetic acid-producing bacterium present on sugar-rich substrates such as such as fruits, flowers and vegetables and traditionally used in the production of fermented food. The preferred living habitat associated with acid conditions makes the structure of the bacterial cell wall interesting to study, due to expected uncommon features. We have used a combination of chemical, analytical and NMR spectroscopy approaches to define the complete structure of the core oligosaccharide from A. pasteurianus CIP103108 LPS. Interestingly, the core oligosaccharide displays a high concentration of negatively charged groups, structural features that might contribute to reinforcing the bacterial membrane.     

Computer-Aided Search for 5-Arylideneimidazolone Anticancer Agents Able To Overcome ABCB1-Based Multidrug Resistance

ABCB1 modulation is an interesting strategy in the search for new anticancer agents that can overcome multidrug resistance (MDR). Hence, 17 new 5-arylideneimidazolones containing an amine moiety, as potential ABCB1 inhibitors, were designed, synthesized, and investigated. The series was tested in both parental (PAR) and multidrug-resistant (MDR) ABCB1-overexpressing T-lymphoma cancer cells using cytotoxicity assays. The ABCB1-modulating activity was examined in rhodamine 123 accumulation tests, followed by Pgp-Glo™ Assay to determine the influence of the most active compounds on ATPase activity. Lipophilic properties were assessed both, in silico and experimentally (RP-TLC). Pharmacophore-based molecular modelling toward ABCB1 modulation was performed. The studies allowed the identification of anticancer agents (p-fluorobenzylidene derivatives) more potent than doxorubicin, with highly selective action on MDR T-lymphoma cells (selectivity index >40). Most of the investigated compounds showed ABCB1-modulating action; in particular, two 5-benzyloxybenzylidene derivatives displayed activity nearly as strong as that of tariquidar.