Novel Hydrogen Sulfide (H2S)-Releasing BW-HS-101 and Its Non-H2S Releasing Derivative in Modulation of Microscopic and Molecular Parameters of Gastric Mucosal Barrier

Hydrogen sulfide (H₂S) is an endogenously produced molecule with anti-inflammatory and cytoprotective properties. We aimed to investigate for the first time if a novel, esterase-sensitive H₂S-prodrug, BW-HS-101 with the ability to release H₂S in a controllable manner, prevents gastric mucosa against acetylsalicylic acid-induced gastropathy on microscopic and molecular levels. Wistar rats were pretreated intragastrically with vehicle, BW-HS-101 (0.5–50 μmol/kg) or its analogue without the ability to release H₂S, BW-iHS-101 prior to ASA administration (125 mg/kg, intragastrically). BW-HS-101 was administered alone or in combination with nitroarginine (L-NNA, 20 mg/kg, intraperitoneally) or zinc protoporphyrin IX (10 mg/kg, intraperitoneally). Gastroprotective effects of BW-HS-101 were additionally evaluated against necrotic damage induced by intragastrical administration of 75% ethanol. Gastric mucosal damage was assessed microscopically, and gastric blood flow was determined by laser flowmetry. Gastric mucosal DNA oxidation and PGE₂ concentration were assessed by ELISA. Serum and/or gastric protein concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, VEGF, GM-CSF, IFN-γ, TNF-α, and EGF were determined by a microbeads/fluorescent-based multiplex assay. Changes in gastric mucosal iNOS, HMOX-1, SOCS3, IL1-R1, IL1-R2, TNF-R2, COX-1, and COX-2 mRNA were assessed by real-time PCR. BW-HS-101 or BW-iHS-101 applied at a dose of 50 μmol/kg protected gastric mucosa against ASA-induced gastric damage and prevented a decrease in the gastric blood flow level. H₂S prodrug decreased DNA oxidation, systemic and gastric mucosal inflammation with accompanied upregulation of SOCS3, and EGF and HMOX-1 expression. Pharmacological inhibition of nitric oxide (NO) synthase but not carbon monoxide (CO)/heme oxygenase (HMOX) activity by L-NNA or ZnPP, respectively, reversed the gastroprotective effect of BW-HS-101. BW-HS-101 also protected against ethanol-induced gastric injury formation. We conclude that BW-HS-101, due to its ability to release H₂S in a controllable manner, prevents gastric mucosa against drugs-induced gastropathy, inflammation and DNA oxidation, and upregulate gastric microcirculation. Gastroprotective effects of this H₂S prodrug involves endogenous NO but not CO activity and could be mediated by cytoprotective and anti-inflammatory SOCS3 and EGF pathways.     

6-Benzylaminopurine Alleviates the Impact of Cu2+ Toxicity on Photosynthetic Performance of Ricinus communis L. Seedlings

Copper (Cu) is an essential element involved in various metabolic processes in plants, but at concentrations above the threshold level, it becomes a potential stress factor. The effects of two different cytokinins, kinetin (KIN) and 6-benzylaminopurine (BAP), on chlorophyll a fluorescence parameters, stomatal responses and antioxidation mechanisms in castor (Ricinus communis L.) under Cu²⁺ toxicity was investigated. Ricinus communis plants were exposed to 80 and 160 μM CuSO₄ added to the growth medium. Foliar spraying of 15 μM KIN and BAP was carried out on these seedlings. The application of these cytokinins enhanced the tissue water status, chlorophyll contents, stomatal opening and photosynthetic efficiency in the castor plants subjected to Cu²⁺ stress. The fluorescence parameters, such as Fm, Fv/Fo, Sm, photochemical and non-photochemical quantum yields, energy absorbed, energy trapped and electron transport per cross-sections, were more efficiently modulated by BAP application than KIN under Cu²⁺ toxicity. There was also effective alleviation of reactive oxygen species by enzymatic and non-enzymatic antioxidation systems, reducing the membrane lipid peroxidation, which brought about a relative enhancement in the membrane stability index. Of the various treatments, 80 µM CuSO₄ + BAP recorded the highest increase in photosynthetic efficiency compared to other cytokinin treatments. Therefore, it can be concluded that BAP could effectively alleviate the detrimental effects of Cu²⁺toxicity in cotyledonary leaves of R. communis by effectively modulating stomatal responses and antioxidation mechanisms, thereby enhancing the photosynthetic apparatus’ functioning.     

Polyaniline–rhodium composites: Preparation,physicochemical characterization,and catalytic properties

In this work, polyaniline (PANI)–rhodium composites have been obtained for the first time. Their preparation procedure has involved reduction of Rh³⁺ ions in RhCl₃ aqueous solutions with NaBH₄ in the presence of PANI. Using UV–vis spectroscopy, it has been found that the reduction process is fast. X‐ray diffraction and Rh3d XPS studies have confirmed that metallic rhodium is incorporated into PANI matrix. SEM and TEM investigations allowed to establish that the sizes of Rh crystallites formed depend on the amount of metal in the composite as well as on the preparation conditions. It has been demonstrated that the composites containing Rh nanoparticles whose size is predominantly below 10 nm can be obtained. IR spectroscopy has proved that PANI chain is protonated in the Rh³⁺ reduction process. Catalytic properties of PANI–Rh composites have been investigated using isopropyl alcohol conversion as the test reaction. It has been found that the composites containing Rh nanoparticles show high redox activity. Catalytic activity of the composites in which larger, agglomerated metal particles have been present is about three times lower. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Part II: surface-enhanced Raman spectroscopy investigation of methionine containing heterodipeptides adsorbed on colloidal silver

Surface-enhanced Raman scattering (SERS) spectra of methionine (Met) containing dipeptides: Met-X and X-Met, where X is: L-glycine (Gly), L-leucine (Leu), L-proline (Pro), and L-phenylalanine (Phe) are reported. Using pre-aggregated Ag colloid we obtained high-quality SERS spectra of these compounds spontaneously adsorbed on colloidal silver. Additionally, we measured Raman spectra (RS) of these heterodipeptides in a solid state as well as in acidic and basic solutions. The RS and SERS spectra of Met-X and X-Met presented in this work appear to be different. One of the most prominent and common features in the SERS spectra of all these dipeptides is a band in the 660-690 cm(-1) range that is due to the C-S stretching, v(CS), vibration of Met. This suggests that all the abovementioned compounds adsorb on the silver surface through a thioether atom. On the other hand, the SERS spectra of X-Met show clearly that not only the S atom but also the carboxylate group interact with the colloid surface as manifested by the enhancement of bands in the 920-930 and 1380-1396 cm(-1) regions. These bands are ascribed to the v(C-COO(-)) and v(sym)(COO(-)) vibrations, respectively. Additionally, a SERS spectrum of Phe-Met indicates that the interaction of the thioether atom, amine group, and aromatic side chain with the silver surface is favorable and may dictate the orientation and conformation of adsorbed peptide.     

Direct Catalytic Asymmetric Aldol Reactions Assisted by Zinc Complex in the Presence of Water

A combination of zinc triflate and chiral C₂‐symmetrical prolinamide ligand leads to high enantioselectivities in direct aldol reactions essentially assisted by water. The presence of 5 mol % of the catalyst affords an asymmetric intermolecular aldol reaction between unmodified ketones and aldehydes to give anti‐products with excellent enantioselectivities ranging from 86–98 % ee. The same bis(prolinamide) ligand is found to catalyze the direct aldol reactions in the presence of water (or in water) with excellent stereocontrol and furnish the corresponding aldols in up to 99 % ee. For the demonstrated catalytic systems organic solvent‐free conditions are applied.     

Effects of Trichoderma harzianum on Photosynthetic Characteristics and Fruit Quality of Tomato Plants

The beneficial role of fungi from the Trichoderma genus and its secondary metabolites in promoting plant growth, uptake and use efficiency of macronutrients and oligo/micro-nutrients, activation of plant secondary metabolism and plant protection from diseases makes it interesting for application in environmentally friendly agriculture. However, the literature data on the effect of Trichoderma inoculation on tomato fruit quality is scarce. Commercially used tomato cultivars were chosen in combination with indigenous Trichodrema species previously characterized on molecular and biochemical level, to investigate the effect of Trichoderma on photosynthetic characteristics and fruit quality of plants grown in organic system of production. Examined cultivars differed in the majority of examined parameters. Response of cultivar Gružanski zlatni to Trichoderma application was more significant. As a consequence of increased epidermal flavonols and decreased chlorophyll, the nitrogen balance index in leaves has decreased, indicating a shift from primary to secondary metabolism. The quality of its fruit was altered in the sense of increased total flavonoids content, decreased starch, increased Bioaccumulation Index (BI) for Fe and Cr, and decreased BI for heavy metals Ni and Pb. Higher expression of swolenin gene in tomato roots of more responsive tomato cultivar indicates better root colonization, which correlates with observed positive effects of Trichodrema.     

IFNβ-Induced CXCL10 Chemokine Expression Is Regulated by Pellino3 Ligase in Monocytes and Macrophages

IFN-I is the key regulatory component activating and modulating the response of innate and adaptive immune system to bacterial as well as viral pathogens. IFN-I promotes the expression of IFN-induced genes (ISG) and, consequently, the production of chemokines, e.g., CXCL10. Those chemokines control migration and localization of immune cells in tissues, and, thus, are critical to the function of the innate immune system during infection. Consequently, the regulation of IFN-I signaling is essential for the proper induction of an immune response. Our previous study has shown that E3 ubiquitin ligase Pellino3 positively regulates IFNβ expression and secretion. Herein, we examined the role of Pellino3 ligase in regulating CXCL10 expression in response to IFNβ stimulation. Our experiments were carried out on murine macrophage cell line (BMDM) and human monocytes cell line (THP-1) using IFNβ as a IFNAR ligand. We demonstrate that Pellino3 is important for IFNβ-induced phosphorylation and nuclear translocation of STAT1/STAT2/IRF9 complex which interacts with CXCL10 promoter and enhances its expression. In this study, we characterize a novel molecular mechanism allowing Pellino3-dependent modulation of the IFNβ-induced response in BMDM and THP-1 cell lines.