Nitric Oxide-Releasing Bacterial Cellulose/Chitosan Crosslinked Hydrogels for the Treatment of Polymicrobial Wound Infections

Polymicrobial wound infections are a major cause of infectious disease-related morbidity and mortality worldwide. In this study, we prepared a nitric oxide (NO)-releasing oxidized bacterial cellulose/chitosan (BCTO/CHI) crosslinked hydrogel to effectively treat polymicrobial wound infections. Linear polyethyleneimine diazeniumdiolate (PEI/NO) was used as the NO donor. The aldehyde group of BCTO and the amine of CHI were used as crosslinked hydrogel-based materials; their high NO loading capacity and antibacterial activity on the treatment of polymicrobial-infected wounds were investigated. The blank and NO-loaded crosslinked hydrogels, namely BCTO-CHI and BCTO-CHI-PEI/NO, were characterized according to their morphologies, chemical properties, and drug loading. BCTO-CHI-PEI/NO exhibited sustained drug release over four days. The high NO loading of BCTO-CHI-PEI/NO enhanced the bactericidal efficacy against multiple bacteria compared with BCTO-CHI. Furthermore, compared with blank hydrogels, BCTO-CHI-PEI/NO has a favorable rheological property due to the addition of a polymer-based NO donor. Moreover, BCTO-CHI-PEI/NO significantly accelerated wound healing and re-epithelialization in a mouse model of polymicrobial-infected wounds. We also found that both crosslinked hydrogels were nontoxic to healthy mammalian fibroblast cells. Therefore, our data suggest that the BCTO-CHI-PEI/NO developed in this study improves the efficacy of NO in the treatment of polymicrobial wound infections.

Fabrication and Characterization of Functional pH-Responsive Poly (S-Co-DEAMVA)-g-Tryptophan

Vanillin was used to synthesize cationic monomers from the amine group with a tertiary amine. It has both an amine and an aldehyde group. For that, it helps graft to form Schiff base with amino acid-like tryptophan. It is abbreviated by {2-[(diethylamino) methyl]-4-formyl-6-methoxyphenyl acrylate} DEAMVA and evaluated by, e.g., 1H NMR, 13C NMR, and FT IR results were compared with the chemical structure elevated good agreement. 10 and 25 mol % of vanillin monomer was copolymerized with (S). The copolymers of poly (S-co-DEAMVA) were investigated by 1H NMR, FTIR, GPC, and DSC. The grafting with tryptophan has also been modified and exposed to the same investigation methods; further, UV/Vis spectroscopy has designated the pH responsiveness. The study aims to improve the general characterization of polystyrene and produce functional pH-responsive polymer for graft biological molecules in the future.

INVESTIGATION OF THE POSSIBILITY OF USING THE METHOD OF DIFFERENTIAL SPECTROPHOTOMETRY FOR THE ANALYSIS OF OVERLAPPING ABSORPTION BANDS OF TRITERPENE SAPONINS CHROMOPHORES AND THEIR QUANTITATIVE DETERMINATION IN AQUEOUS SOLUTIONS

A detailed analysis of the absorption spectra of mono- and bidesmoside triterpene glycosides was performed. It is suggested that the maximum in the region of 198–208 nm is attributed to the absorption of the double bond in the cyclohexene ring of the aglycone. The second less seen maximum at a wavelength of 280 nm is observed in the spectrum of saponin Quillaja Saponaria and is almost completely absent in the spectrum of saponin Mukorossi Sapindus. Identification of this maximum is extremely difficult, since its presence can be due to both the aldehyde group in the aglycone and the hydroxyl and carboxyl groups in the carbohydrate molecules. Using the method of differential spectrophotometry, a method for decomposing the UV spectrum of saponins into its constituent components is proposed and justified. A spectral analysis was performed, including the assignment of the absorption bands to the functional groups of the studied compounds. The possibility of estimating changes in the spectral properties of glycoside solutions with changes in the acidity of the medium is considered. The possibility of a bathochromic shift of the maximum absorption of the aglyconic part of saponin depending on the microenvironment (the structure of the carbohydrate part) and changes in the pH of the solution is established. It is shown that the bands at 274, 280.5 nm correspond to n-π* transitions of carbonyl and carboxyl groups and are determined only in the regions of high concentrations in Quillaja Saponaria saponin solutions. Based on the results obtained, calibration models for the quantitative determination of saponins in solutions are proposed. The regression analysis of the calibration equations is carried out, the main statistical indicators are calculated.

Methylglyoxal Levels in Human Colorectal Precancer and Cancer: Analysis of Tumor and Peritumor Tissue

Colorectal cancer (CRC) is one of the most common cancers worldwide and its incidence is increasing; therefore, an understanding of its oncogenic mechanisms is critical for improving its treatment and management. Methylglyoxal (MGO) has a highly reactive aldehyde group and has been suggested to play a role in oncogenesis. However, no standardized data are currently available on MGO levels in colorectal precancerous and cancerous lesions. We collected 40 matched colorectal tumor and peritumor tissues from patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive cancer (IC). MGO levels increased between LGD, HGD, and IC tumor tissues (215.25 ± 39.69, 267.45 ± 100.61, and 587.36 ± 123.19 μg/g protein, respectively; p = 0.014). The MGO levels in peritumor tissue increased and were significantly higher than MGO levels in tumor tissue (197.99 ± 49.40, 738.09 ± 247.87, 933.41 ± 164.83 μg/g protein, respectively; p = 0.002). Tumor tissue MGO levels did not correlate with age, sex, underlying disease, or smoking status. These results suggest that MGO levels fluctuate in progression of CRC and warrants further research into its underlying mechanisms and function in tumor biology.

Fluctuation In the Phase Transition Temperature of Poly (NIPAAm-co-HEMA-co-DMAMVA)-Post-guanine Affected by Hydrophilic/hydrophobic Interaction: Fabrication and Characterizations

The phase separation and transition temperature of poly (N-isopropylacrylamide) have been developed by the terpolymerization with new pH-responsive monomer and highly hydrophilic 2-Hydroxyethyl methacrylate. The new monomer based on vanillin is called 2-((dimethylamino)methyl)-4-formyl-6-methoxyphenyl acrylate (DMAMVA), and is investigated by chemical methods (1H, 13C NMR, FTIR, and mass spectroscopy). Terpolymers of dual-responsive thermo-pH with functional groups were fabricated via free radical polymerization of N-isopropylacrylamide (NIPAAm), 10 mol% 2-Hydroxyethyl methacrylate (HEMA), and 5, 10, and 20 mol% DMAMVA. A selected terpolymer was used for post-polymerization with guanine via click reaction and the formation of an imine between the aldehyde group of DMAMVA and the amine group of guanine. All terpolymer and post-terpolymer are chemically evaluated. The physical properties have been implemented by GPC (molecular weight and dispersity), DSC (glass transition temperature Tg), TGA (steps of degradation), and SEM (morphological features). The fluctuations in phase transition temperature Tc or the lower critical solution temperature LCST of the polymer solution in different pH solutions have been performed by two methods, first, the turbidity test by UV-Vis-spectroscopy, second, by micro-DSC for aqueous polymer solution. This work will be extended for more applications in bio-separation technology.

An oxidative metabolic pathway of 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEHU) from alginate in an alginate-assimilating bacterium

Alginate-assimilating bacteria degrade alginate into an unsaturated monosaccharide, which is converted into 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEHU). DEHU is reduced to 2-keto-3-deoxy-D-gluconate by a DEHU-specific reductase using NAD(P)H. This is followed by pyruvate production via the Entner-Doudoroff pathway. Previously, we identified FlRed as a DEHU reductase in an alginate-assimilating bacterium, Flavobacterium sp. strain UMI-01. Here, we showed that FlRed can also catalyze the oxidation of DEHU with NAD+, producing 2-keto-3-deoxy-D-glucarate (KDGR). FlRed showed a predilection for NADH and NAD+ over NADPH and NADP+, respectively, and the Km value for NADH was approximately 2.6-fold less than that for NAD+. Furthermore, we identified two key enzymes, FlDet and FlDeg, for KDGR catabolism. FlDet was identified as an enzyme of the ribonuclease activity regulator A family, which converts KDGR to α-ketoglutaric semialdehyde (α-KGSA). FlDeg, a type II α-KGSA dehydrogenase, generated α-ketoglutaric acid by oxidizing the aldehyde group of α-KGSA using NAD(P)+. Consequently, unlike the conventional DEHU reduction pathway, DEHU can be directly converted to α-ketoglutaric acid without consuming NAD(P)H. Alginate upregulated the expression of not only FlRed and two enzymes of the DEHU-reduction pathway, but also FlDet and FlDeg. These results revealed dual pathways of DEHU metabolism involving reduction or oxidation by FlRed.

Nostocyclopeptides as New Inhibitors of 20S Proteasome

Nostocyclopeptides (Ncps) are a small class of bioactive nonribosomal peptides produced solely by cyanobacteria of the genus Nostoc. In the current work, six Ncps were isolated from Nostoc edaphicum strain CCNP1411. The bioactivity of these compounds was tested in vitro against 20S proteasome, a proteolytic complex that plays an important role in maintaining cellular proteostasis. Dysfunction of the complex leads to many pathological disorders. The assays indicated selective activity of specific Ncp variants. For two linear peptide aldehydes, Ncp-A2-L and Ncp-E2-L, the inhibitory effects on chymotrypsin-like activity were revealed, while the cyclic variant, Ncp-A2, inactivated the trypsin-like site of this enzymatic complex. The aldehyde group was confirmed to be an important element of the chymotrypsin-like activity inhibitors. The nostocyclopeptides, as novel inhibitors of 20S proteasome, increased the number of natural products that can be considered potential regulators of cellular processes.

A Novel Class of Norovirus Inhibitors Targeting the Viral Protease with Potent Antiviral Activity In Vitro and In Vivo

Human noroviruses (HuNoVs) are the most common cause of viral gastroenteritis resulting annually in ~219,000 deaths and a societal cost of ~USD 60 billion, and no antivirals or vaccines are available. Here, we assess the anti-norovirus activity of new peptidomimetic aldehydes related to the protease inhibitor rupintrivir. The early hit compound 4 inhibited the replication of murine norovirus (MNV) and the HuNoV GI.1 replicon in vitro (EC50 ~1 µM) and swiftly cleared the HuNoV GI.1 replicon from the cells. Compound 4 still inhibits the proteolytic activity. We selected a resistant GI.1 replicon, with a mutation (I109V) in a highly conserved region of the viral protease, conferring a low yield of resistance against compound 4 and rupintrivir. After testing new derivatives, compound 10d was the most potent (EC50 nanomolar range). Molecular docking indicated that the aldehyde group of compounds 4 and 10d bind with Cys139 in the HuNoV 3CL protease by a covalent linkage. Finally, compound 10d inhibited the replication of HuNoV GII.4 in infected zebrafish larvae, and PK studies in mice showed an adequate profile.

Asymmetric phthalocyanine compounds in the structure D-π-A containing cyano groups: Design, synthesis and dye-sensitized solar cell applications

In this study, asymmetric zinc phthalocyanine compounds with Donor-π-Anchor (D-π-A) property that enable the movement of electrons in molecular structure in one direction were synthesized. Phthalocyanines were designed to ensure electron mobility within the molecule and to facilitate the transfer of electrons to the TiO2 layer. The synthesized asymmetric zinc phthalocyanines (ZnPc-1 and ZnPc-2) are molecules with three donor biphenyls and one anchor aldehyde group and three acceptor/anchor cyano and one anchor aldehyde group, respectively. The effect of biphenyl and cyano groups on cell efficiency with aldehyde anchor group was investigated. The structure of the synthesized phthalocyanines was characterized by Fourier Transform Infrared Spectrometry (FTIR), Mass Spectrometry (MS), UV-vis, Fluorescence spectroscopy. The experimentally calculated optical band gap values were supported by the values found by Density Functional Theory (DFT) calculations. dye sensitive solar cells were measured and the efficiencies were evaluated with reference to the N719 standard dye. In the solar cell measurements of the designed phthalocyanines, the structure containing the cyano group has been given a higher photovoltaic cell thanks to the higher short circuit photo-current (Jsc). In this way, the highest power conversion efficiency value was achieved among the cyano group molecules.

A convenient synthetic approach to obtain meso-Uracil-BODIPY

An effective and convenient protocol for the synthesis of 1-Substituted-6-formyl-uracil derivatives has been developed. A three-step sequence has allowed obtaining new 6-Formyl uracil with various substituents at N-1, in large quantity using low-cost precursors. Uracil molecules containing an aldehyde group have been used as useful precursors for the preparation of meso-(1’-Substituted-6’-uracil)-BODIPY derivatives. In this way, regioselectively functionalized BODIPYs directly connected to a nucleobase were prepared in yields from 30 to 45%. MALDI-TOF mass spectrometry, NMR, UV-vis absorption, steady-state and time-resolved fluorescence spectroscopies have been used to characterize the structures and the spectroscopic/photophysical properties of the obtained dyes.