Malonic Acid Research Articles

Quality Assurance System when Studying the Pharmacological Safety of Etmaben

Quality assurance plays a key role in preclinical research, where every detail must be strictly controlled and verified. Standard operating procedures are essential part of any quality assurance system, defining precisely the steps and methods of implementing certain tasks or processes in a laboratory. In this article, the main components of a quality assurance system are discussed using the example of studying the pharmacological safety of a malonic acid derivative.

Impact of Serum Folate and Vitamin B12 on Mental Health in Patient Admitted at Razi Psychiatric Hospital

Vitamin B12 (cobalamin) is one of the essential vitamins that affect various systems in the body, including the central nervous system and plays an important role in the metabolism of the nervous system, although its exact role under pathological conditions is not fully understood. The present study aimed to assessing vitamin B12 & serum folate in patient admitted at Razi psychiatric hospital. A cross section study subjects were inpatients with psychiatric disorder, patients from 21 to 60 years old. In this group of 40 psychiatric patients, there is no evidence of clinically relevant changes in serum vitamin B12 and folate level. Vitamin B12 deficiency can occur despite “normal” serum cobalamin levels; therefore, measuring homocysteine and methyl malonic acid can decrease false-negative findings.

Altering the Solid Electrolyte Interface Through Surface-Modification of Lithium Metal Anode for High-Voltage Lithium Battery

Abstract The physical structure and chemical composition of the solid electrolyte interphase (SEI) affect the performance of the lithium metal anode. The tuning of the chemical composition and structure of the SEI through the surface modification of the lithium metal anode has been conducted. A series of dicarboxylic acids, oxalic acid, malonic acid, succinic acid, glutaric acid, and adipic acid have been utilized to modify the surface of the lithium anode. Physical characterization methods have been employed to study the surface morphology and chemical composition of the SEI. Symmetrical (Li/Li) and asymmetrical (NMC622/Li) cells with pristine lithium and surface modified lithium electrodes have been assembled and tested. NMC622/Li cell with surface modified lithium shows improved performance compared to that of pristine lithium. Malonic acid-treated lithium outperforms all the electrodes by retaining 141 mAh/g specific capacity even after 100 cycles of charge-discharge. XPS depth profiling analysis reveals that the SEI on the MA-Li contains evenly distributed organic and inorganic components which are responsible for the performance of MA-Li.

Electrochemical DNA Sensor Based on Poly(proflavine) Deposited from Natural Deep Eutectic Solvents for DNA Damage Detection and Antioxidant Influence Assessment

Electrochemical DNA sensors for DNA damage detection based on electroactive polymer poly(proflavine) (PPFL) that was synthesized at screen-printed carbon electrodes (SPCEs) from phosphate buffer (PB) and two natural deep eutectic solvents (NADESs) consisting of citric or malonic acids, D-glucose, and a certain amount of water (NADES1 and NADES2) were developed. Poly(proflavine) coatings obtained from the presented media (PPFLPB, PPFLNADES1, and PPFLNADES2) were electrochemically polymerized via the multiple cycling of the potential or potentiostatic accumulation and used for the discrimination of thermal and oxidative DNA damage. The electrochemical characteristics of the poly(proflavine) coatings and their morphology were assessed using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM). The working conditions for calf thymus DNA implementation and DNA damage detection were estimated for all types of poly(proflavine) coatings. The voltammetric approach made it possible to distinguish native and chemically oxidized DNA while the impedimetric approach allowed for the successful recognition of native, thermally denatured, and chemically oxidized DNA through changes in the charge transfer resistance. The influence of different concentrations of conventional antioxidants and pharmaceutical preparations on oxidative DNA damage was characterized.

Cocrystal screening of benznidazole based on electronic transition, molecular reactivity, hydrogen bonding, and stability.

Screening of cocrystals of active pharmaceutical ingredients is important in the development of pharmaceutical compounds because it improves bioavailability, stability, solubility, and many other physicochemical properties. In this work, quantum chemical calculations were utilized for the computational evaluation of the cocrystal screening of benznidazole (BZN) API via hydrogen bonding with four coformers (maleic acid, malonic acid, oxalic acid, and salicylic acid), and they contain carboxylic groups. The nitrogen of the imidazole ring in benznidazole and the carboxylic group of the coformer form a hetero-synthon connected by a strong hydrogen bond. The strength of the hydrogen bonding interaction O-H…N was measured using various tools. It was found that in comparison to BZN cocrystals with malonic acid, oxalic acid, and salicylic acid, the O-H…N interaction in the BZN-maleic acid cocrystal had higher interaction energy, indicating it had stronger hydrogen bonding. The strength of the hydrogen bond O-H…N for synthons was discovered to be more beneficial than the C-H…O interaction, as confirmed by ESP analysis. The BZN-salicylic acid cocrystal was found to be more reactive and polarizable, whereas the BZN-malonic acid cocrystal was more stable. Cocrystals of benznidazole exhibited better physicochemical characteristics than API benznidazole, as indicated by electron transition properties between the most significant orbitals. The computational evaluation for the screening of benznidazole cocrystals was performed in Gaussian 16 software using density functional theory (DFT) with the hybrid functional B3LYP and the basis set 6-311 + + G(d,p). The UV-Vis absorption spectrum in solvent water was analyzed using the TD-DFT/6-311 + + G(d,p) method to determine the influence of the solvent in cocrystals using a polarizable continuum model. The strength of the hydrogen bonding interactions O-H…N in each of those mentioned cocrystals was used to screen the cocrystals using tools such as thermodynamic probability, ESP analysis, QTAIM analysis, and NBO analysis. The pairing energy of interaction was measured by determining H-bond donor ( ) and H-bond acceptor ) parameters for hydrogen bonds from maxima and minima on the ESP surface. GaussView 06 software was used to create, visualize, and plot the optimized structure of the cocrystal and HOMO-LUMO orbitals. The AIMALL (10.05.04) software package generated the molecular graph for intra- and intermolecular interactions. The RDG-scatter plot, MEP map, and ELF plot were rendered from Multiwfn 8.0 and VMD 1.9.1 software.

An Enantioselective Decarboxylative Glycolate Aldol Reaction.

Herein, we report the application of a benzyloxy-functionalized malonic acid half thioester as an activated ester equivalent in a highly enantioselective decarboxylative glycolate aldol reaction. This robust method operates at ambient temperature, tolerates air and moisture, and generates CO2 as the only byproduct. The synthetic applicability of the method is demonstrated by the large-scale enantiodivergent synthesis of α-benzyloxy-β-hydroxybutyric acid thioester and its subsequent conversion to diverse polyoxygenated building blocks, deoxy-sugars, and (-)-angiopterlactone B.

Study on Several Novel Crystalline Complexes of Sorafenib with Dicarboxylic Acid: Nature Identification and Solubilization Mechanism

The development of solid-state forms of drugs is an effective approach to increase solubility. This study developed three crystalline complexes of sorafenib (SF) with oxalic acid (OA) and malonic acid (MA) using a solvent method, named SF+·OA-·THF, SF+·OA-, and SF-MA. The formation of these complexes was influenced by the crystalline method, solvent polarity, and the carbon chain length of the dicarboxylic acids. Single-crystal X-ray diffraction revealed proton transfer in SF+·OA-·THF, classifying it as a channel-type salt solvate and conformational polymorph due to hydrogen bond formation. 13C solid-state nuclear magnetic resonance and X-ray photoelectron spectroscopy confirmed proton transfer in SF+·OA-·THF and SF+·OA-, but not in SF-MA, indicating that SF+·OA- is a salt while SF-MA is a co-crystal. Fourier Transform Infrared Spectroscopy further supported these findings. Compared with Form Ⅰ, SF+·OA-, SF+·OA-·THF, and SF-MA increased the apparent solubility of SF by 8.3, 7.9, and 6.4 times in pH 1.2 HCl buffer, and by 4.0, 3.1, and 4.5 times in pH 6.8 PBS buffer, respectively. All crystalline complexes exhibited a “spring and parachute” phenomenon due to the solubility difference between the drug and the dicarboxylic acids. Notably, the intermolecular forces between SF and THF in SF+·OA-·THF prolonged the “spring and parachute” process. Additionally, these crystalline complexes demonstrated good stability. This study provides valuable insights into the development and identification of crystalline complexes and their dissolution mechanisms.

Micronutrient intake and status in young vegans, lacto-ovo-vegetarians, pescatarians, flexitarians, and omnivores.

Whether youth who follow plant-based diets in Nordic countries meet their dietary needs for micronutrients remains unclear. This study aims to evaluate micronutrient intake and status in Norwegian youth following vegan, lacto-ovo-vegetarian, pescatarian, flexitarian and omnivore diets. Cross-sectional design, with healthy 16-to-24-year-olds (n = 165). Participants were asked to complete a questionnaire and four 24-hour dietary recalls. Dried blood spots (DBS) and spot-urine samples were collected for analysis of methyl malonic acid (MMA) (n = 65), haemoglobin (Hb) (n = 164) and urinary iodine concentration (UIC) (n = 163). Vegans reported highest habitual supplement usage of multivitamin (58%), B12 (90%) and macroalgae consumption (32%), while flexitarians reported highest habitual usage of omega-3 supplements (56%). For daily supplement usage, vegans reported highest use of multivitamins (42%), B12 (79%), iodine (37%) and iron (63%). Increased risk of inadequate intake (energy-adjusted) were found for vitamin D (60% within lacto-ovo-vegetarians), selenium (70% within lacto-ovo-vegetarians, 65% within omnivores), and iodine (63% within vegans). Median MMA levels suggest low risk of insufficient B12 status across all groups (MMA 0.04‒0.37µmol/l) and 2% had MMA levels indicating possible B12 deficiency and 8% had elevated levels. Median Hb levels indicated low risk of anemia across all groups (≥ 12.0 females, ≥ 13.0g/dl males), though 7% had Hb values indicating risk of mild anemia and 4% risk of moderate anemia. The median UIC indicates mild iodine deficiency in all groups (UIC < 100µg/l), except vegans, who were moderately iodine deficient (UIC < 50µg/l). Our study indicated that the participating youth had low risk of inadequate intake of most micronutrients, partly due to high supplement usage. However, for iodine, vitamin D, and selenium higher risk of inadequate intake was found. UIC corroborated the low iodine intake among vegans. Thus, we suggest iodine status of youth in Norway should be monitored, especially among young fertile women who omits dietary iodine sources, until a mandatory iodine fortification program is implemented. Furthermore, we suggest that food education on how to secure sufficient nutrients from food in general should be provided to the Norwegian youth population, especially how to secure adequate intake of vitamin D, selenium and iodine.

Design, Synthesis, and Anti-Prostate Cancer Potential of 2-(4-Nitrobenzyl) Malonates In Vitro and DAL Acute Oral Toxicity Assessment In Vivo.

New 4-nitrobenzyl derivatives were designed and synthesised by nucleophilic substitution reactions of 4-nitrobenzyl bromide with malonic acid and its derivatives. The synthesised molecules were characterised using mass analysis and spectroscopic techniques and tested for their antioxidant properties using various methods, such as nitric oxide, DPPH, and hydrogen peroxide radical scavenging methods. The anti-inflammatory activities of the molecules were assessed using RBC membrane stabilisation and albumin denaturation methods. We evaluated the compounds' potential anti-prostate cancer activity using the DU145 cell line. The MTT assay determined the cell viability, indicating good anti-proliferative activity. The molecule 3 c exhibited the highest potency, with a CTC50 of 11.83 μg/mL. Molecular dynamics simulations were performed to study the stability of the ligand within the protein after docking and the resulting protein-ligand complex. The in vivo analysis of molecule 3 c in the DAL xenograft model demonstrated promising results. The increase in life span, reduction in tumor volume, and comparable effects to standard drugs are encouraging features that suggest that molecule 3 c may possess significant potential as an anti-cancer agent. The research also implies that these molecules might be potential lead compounds for developing new prostate cancer drugs.

Probing the role of hydrogen bond donors on the speciation and electrochemical behavior of Eu(III) in choline chloride-based DESs

This study explores the electrochemical properties and speciation of Eu(III) ions in choline chloride (ChCl)-based deep eutectic solvents (DESs), focusing on how different hydrogen bond donors—urea (U), ethylene glycol (EG), and malonic acid (MA)—influence the stability of europium complexes. Employing electrochemical methods, spectroscopic analysis, and theoretical approaches, the research examines how changes in hydrogen bonding during complexation affect Eu(III) coordination. Cyclic voltammetry highlights the role of complex formation and DES viscosity in controlling mass transport and electron transfer rates. Theoretical and experimental data show that the ChCl:1MA DES forms the most stable europium complex, driven by strong hydrogen bonding and robust Eu-DES interactions, as supported by optimized geometries and favorable electrochemical stability. This stability is further confirmed by the high negative binding and formation free energies of Eu(NO3)3·5H2O in all three DES systems. Photoluminescence spectroscopy reveals fluorophore formation due to interactions between hydrogen bonds and functional groups such as –NH2, –COOH, and –OH, enhancing the understanding of Eu3+-DES complexes for potential applications in materials science. By clarifying how hydrogen bond donors affect Eu(III) speciation and reactivity, this research advances lanthanide chemistry in DESs and opens avenues for designing Eu(III)-based materials with specialized properties for various technological uses.

Extraction optimisation and characterisation of Artocarpus integer peel pectin by malonic acid-based deep eutectic solvents using response surface methodology

Traditional pectin extraction methods involve strong acids, which are environmentally harmful. This study explores an innovative approach using Malonic Acid (MA)-based Deep Eutectic Solvents (DES) to extract pectin from Artocarpus integer Peel (AIPP), optimised through Response Surface Methodology (RSM). The extracted AIPP-A and AIPP-B from ChCl-MA and ChDHCit-MA DES, respectively, were characterised for yield, pH, solubility, Degree of Esterification (DE), Water and Oil Holding Capacity (WHC and OHC). The experimental values aligned with RSM model predictions, with low standard deviations: 0.7300 for ChCl-MA and 0.1531 for ChDHCit-MA. Optimal extraction conditions for AIPP-A were 3.27 % ChCl-MA, 1.28 h extraction time, 50.44 °C temperature, and a 1:40 g/mL solid-to-liquid ratio. For AIPP-B, the conditions were 4.95 % ChDHCit-MA, 2.04 h extraction time, 79.65 °C temperature, and a 1:50 g/mL solid-to-liquid ratio. ChCl-MA yielded 30.97 % AIPP, which was higher than that of ChDHCit-MA (27.99 %). Both AIPP demonstrated desirable properties such as low pH, high solubility, and significant DE. AIPP-A exhibited a greater DE (58.40 %) compared to AIPP-B (32.4 %) contributed to its lower WHC and higher OHC. In conclusion, RSM-based optimisation of AIPP extraction with DES is effective in producing pectin that is suitable for use as a gelling agent, preservative, and stabiliser in the food industry.

PSLBI-22 Identifying plasma metabolites influencing body weight in Salmonella challenged growing pigs: A machine learning approach

Abstract Body weight (BW) is an important component of pig productivity. Understanding the metabolic factors affecting growth rate is key to guiding nutritional strategies and bringing economic benefits to pig farms. Machine learning (ML) algorithms have been used to capture patterns in large datasets and predict animal production traits based on integrated information of performance data and blood records. However, utilizing ML models and metabolomic profiling to predict BW of pigs in small datasets with challenged animals has yet to be reported. Therefore, this study investigated use of plasma metabolites in predicting BW of pigs at the growing stage. This simulation used data from gilts (n = 40; BW = 25.6 ± 2.3 kg) raised over a 28-d trial. Plasma samples and BW were collected on d 0, 14, and 28 after 8 h of fasting. Ninety plasma metabolites were identified and quantified from an untargeted metabolomics assay. The development dataset included 30, and the validation dataset contained 10 unique animals with repeated measures in time. The metabolites were log-transformed, Pareto-scaled and missing values were imputed using the minimum nonzero value method. The BW prediction model was performed in R with the caret package. The optimal hyper-parameter configuration for the random forest and neural network algorithms was evaluated based on repeated cross-validation. The final model was the random forest composed of 400 trees with 45 randomly selected predictors. Model accuracy was estimated on repeated cross-validation with 10-folds and 5 repeats and compared with the validation set based on the coefficient of determination (R2), the root mean squared error (RMSE), and Pearson correlation (r). The metabolites with greater contribution with variable importance score above 10 to the model development were extracted. Aiming to understand differences in BW categories, the model response was visualized with an alluvial diagram for the 3 variables with the greatest metabolite importance, and BW was classified as high, medium, and low. The main metabolites driving BW were lysine, oleic acid, aminomalonic acid, myo-inositol, and linoleic acid. The RMSE after cross-validation was 7.22 kg of BW (r = 0.70), and R2 = 0.39. For pigs with a high BW, the predicted BW was explained by generally less plasmatic concentrations of lysine, oleic acid, and aminomalonic acid. Lysine is the main amino acid for muscle protein accretion, whereas oleic acid is for energy substrate. Aminomalonic acid is a metabolite resulting from glycine metabolism and is important in reversing oxidative damage caused by pathogens. Therefore, decreased plasma lysine, amino malonic acid, and oleic acid may indicate faster growth and lean deposition, leading to heavier BW in pigs. Using random forests helped to connect the plasma dynamics to BW and is a promising avenue to understand the main drivers in BW of group-housed pigs.

Comparison of germanium recovery from copper(II) sulfate-based solution using tertiary amine and oxime extractant

Germanium is considered by many world economies, including the USA and EU, as a critical raw material. One of the methods, which may be used in its recovery is solvent extraction. Using it application of more environmentally harmful processes like tannin concentrate precipitation or chlorination may be reduced. Solvent extraction of germanium from solution after oxidative leaching of copper cake by two extractants, chelating Mextral 63H (LIX 63 equivalent) and basic trioctylamine (TOA), were compared. For TOA influence of complexant addition, tartaric acid, malic acid, malonic acid, and succinic acid, on germanium recovery yield was also tested. It was found that under investigated conditions, i.e. pH∼1.0 TOA was a better and more selective germanium extractant. The highest Ge extraction yields (>96 %) were achieved when tartaric acid was used as a germanium complexant in an aqueous phase. It was determined that germanium may be stripped from the organic phase using > 5 wt% NaOH solution with > 93 % yield.

Enhancing impact resistance in E‐glass fabric composites through shear thickening fluids and functionalized polyethylene glycol

AbstractIn this study, we delved into innovative strategies to make neat E‐glass fabrics (NGFs) more impact‐ and tensile‐resistant by using shear‐thickening fluids (STFs). To achieve this goal, the polyethylene glycol (PEG) in STFs has been modified. Subsequently, the STF‐impregnated fabric composites were prepared from unmodified PEG and functionally modified PEGs using malonic and tartaric acids, V/S/GF, M/S/GF, and T/S/GF composites, respectively. Fourier‐transform infrared spectroscopy (FTIR) analysis was conducted to confirm the chemical modification of PEGs. The rheological tests showed a significant improvement in the peak viscosity of modified STFs compared with virgin STF. Dynamic rheological analysis also studied media‐particle interaction, revealing improved media‐particle interaction in STFs due to abundant H‐bonding. In addition, a series of experimental tests, namely compressive impact resistance and strip tensile strength tests, have been conducted to investigate the effect of STF modification on the NGF. The results revealed notable improvements in tensile strength and energy dissipation in the T/S/GF and M/S/GF composites compared with V/S/GF and NGF. Importantly, this improvement extended to the impact performance of single, triple, and quintuple layers. Notably, we found that the peak load of 5 T/S/GF was 37.71%, 18.57%, and 11.87% lower than that of 5NGF, 5 V/S/GF, and 5 M/S/GF, respectively. The idea that made these improvements possible came from PEG functionalization, which helps hydrogen bonds form between the dispersed phase and the dispersion medium, leading to higher viscosity. This, in turn, increases inter‐yarn friction, effectively enhancing the spring‐like properties of T/S/GF and M/S/GF compared with V/S/GF. A two‐step artificial intelligence regression analysis underpinned these findings, elucidating the interplay of molecular mechanisms in high‐performance fabric composites.

Synthesis of Diethyl 6-Amino-1-aryl-2-oxo-1,2-dihydropyridine-3,5-carboxylate

It was found that the reaction of malonic acid N-arylamidoesters with ethyl 2-cyano-3-ethoxyacrylate in ethanol in the presence of equimolar amounts of triethylamine both at room temperature and under reflux leads to the formation of previously unknown diethyl 6-amino-1-aryl-2-oxo-1,2-dihydropyridine-3,5-carboxylates with yields of 40–70%. Structure of the obtained compounds was confirmed by NMR and IR spectroscopy data. Antibacterial activity of some of the obtained compounds was studied.

Design, synthesis and structure-activity relationship of malonic acid non-nucleoside derivatives as potent CD73 inhibitors

High levels of extracellular adenosine in tumor microenvironment (TME) has extensive immunosuppressive effect. CD73 catalyzes the conversion of AMP into adenosine and regulates its production. Inhibiting CD73 can reduce the level of adenosine and reverse adenosine-mediated immune suppression. Therefore, CD73 has emerged as a valuable target for cancer immunotherapy. Here, a new series of malonic acid non-nucleoside derivatives were designed, synthesized and evaluated as CD73 inhibitors. Among them, compounds 18 and 19 exhibited significant inhibition activities against hCD73 with IC50 values of 0.28 μM and 0.10 μM, respectively, suggesting the feasibility of replacing the benzotriazole moiety in the lead compound. This study explored the novelty and structural diversity of CD73 inhibitors.

Organocatalysis for Enantioselective Decarboxylative Nucleophilic Addition Reactions

AbstractThe catalytic decarboxylation of malonic acid half oxy‐ and thioesters, β‐ketocarboxylic acids, and their related compounds is a straightforward, powerful, and atom‐economical strategy for the in‐situ formation of enolates, which are important and well‐studied synthons for various functional materials and natural products. This strategy, inspired by the biosynthesis of polyketides and fatty acids, is an attractive method for synthesizing enols from carboxyl compounds with less reactive α‐hydrogen atoms under mild conditions. In addition, these reactions are environmentally friendly and are of great interest to chemists because the use of a stoichiometric amount of base can be avoided, and the only byproduct is CO2. Thus far, remarkable progress has been made, especially in the field of organocatalytic enantioselective decarboxylation reactions, allowing for the stereocontrolled formation of new C−H, C−C, C−heteroatom, and C−X bonds. This review provides a comprehensive overview of organocatalytic enantioselective decarboxylation reactions and highlights the significant progress made since 2020. In particular, it focuses on chiral catalyst systems and transition states as key parameters for decarboxylation reactions.

An experimental-computational study on thermodynamic properties and intermolecular interactions of binary mixtures composed of quaternary ammonium salts-based deep eutectic solvents and [ETN] or [ACN]

To deep understand the thermodynamic properties and intermolecular interactions of quaternary ammonium salts-based deep eutectic solvents (DESs), two novel DESs systems ([TPAB]:[MA] and [TBAB]:[MA]) were synthesized using tetrapropylammonium bromide ([TPAB]) or tetrabutylammonium bromide ([TBAB]) as hydrogen bond acceptor (HBA) and malonic acid ([MA]) as hydrogen bond donor (HBD). Then, the ethanol (ETN) and acetonitrile (ACN) were used to prepare four DESs + solvent mixtures. Based on experimental data of density and surface tension of these four binary mixtures, the thermodynamic parameters such as apparent molar volume (Vϕ), excess molar volume (VE), limiting apparent molar expansibility (E0ϕ), molar surface entropy (s), molar surface Gibbs energy (gs), and molar surface enthalpy (h) were calculated. At the same temperature, the calculated VE values of binary mixtures were arranged in the following sequence: [TBAB]:[MA] + [ETN] > [TPAB]:[MA] + [ETN] > [TPAB]:[MA] + [ACN] > [TBAB]:[MA] + [ACN]. Based on the radial distribution functions (RDFs) theory, this observed phenomenon was attributed to the enhanced interaction between HBA and [ETN] in the DESs + [ETN] as compared to the interaction between HBA and [ACN] in the DESs + [ACN]. The predicted surface tension values (γ(pre)) of the four binary mixtures were calculated and highly correlated with the experimental surface tension values (γ(exp)). Moreover, the Br1 atom in [TPAB], the Br2 atom in [TBAB], and the H9 atom in [MA] were selected as reference sites. The interaction strength sequence between HBD and HBA was investigated using RDFs as follows: [TBAB]:[MA] + [ACN] > [TPAB]:[MA] + [ACN] > [TBAB]:[MA] + [ETN] > [TPAB]:[MA] + [ETN]. This study can provide an important theoretical support for further utilization of quaternary ammonium salts-based DESs.

Assessment of Antimicrobial Activity of Chitosan, ZnO, and Urtica dioica-ZnO NPs Against Staphylococcus aureus Isolated from Diabetic Ulcers.

Staphylococcus aureus (S. aureus) is considered as one of the challenging ulcer infections in diabetic patients especially those who have acquired antibiotic-resistant infections. Nanotechnology products have enormous potential to treat diseases including infectious diseases. As chitosan and zinc oxide (ZnO) nanoparticles (NPs) have harbored a high antimicrobial effect, this survey was aimed to synthesize chitosan, ZnO, and ZnO-Urtica. diocia (ZnO-U. diocia) NPs, and to assess their antimicrobial effects and their influence on virulencegenes expression in S. aureus isolates from diabetic ulcers. The antibacterial effect of NPs was detected by microdilution method. The most frequently components in U. diocia aqueous extract were linalool,4-thujanol, camphor, carvacrol, propanedioic acid, and di(butyl) phthalate. More than 95% of clinical S. aureus isolates were resistant to several antibiotics including erythromycin, cefoxitin, clindamycin, and ciprofloxacin. The most resistant isolates were S. aureus ATDS 52, ATDS 53, F5232, and F91. The lowest MIC and MBC by the NPs on the isolates was detected as 0.128 g/mL and 0.178g/mL, respectively. A significant decrease of 90% in the expression rates of lukED and RNAIII genes was reported for S. aureus isolates treated with the NPs. The synthetized ZnO-U. diocia and chitosan NPs can be proposed as a reliable and effective antimicrobial agent targeting diabetic ulcers infections caused by S. aureus because of its high effects on the bacterial growth and virulence genes expression.

Abstract Tu041: Gut microbiome Bifidobacterium is associated with improvement in severity of heart failure with reduced ejection fraction

Background: Heart failure (HF) has been associated with dysregulated gut microbiome. However, less is understood about how gut microbiome alterations relate to changes in HF severity. We sought to understand how gut microbial shifts and associated host signatures related to changes in clinical status of patients with HF with reduced ejection fraction (HFrEF). Methods: Twenty-six adults with HFrEF were recruited and completed 2 study visits approximately 6 months apart. At each visit they provided stool sample for microbiome profiling (metagenomic sequencing), and fasting blood samples for untargeted metabolomics (liquid chromatography–mass spectrometry) and cytokine assay (Luminex antibody-conjugated bead capture). Subjects also completed dietary surveys. Clinical improvement was measured as between-visit change in the New York Heart Association (NYHA) class. Results: Between-visit NYHA class improved in 6 individuals; 20 patients remained stable or worsened. After accounting for demographics, body mass index, and diet, genus Bifidobacterium was significantly enriched in the improved group and increased over time (Figure 1). Bifidobacterium was directly associated with circulating malonic acid, which is implicated in cardio-protection and cardiomyocyte regeneration, and with indole-3-propionate (IPA), anti-inflammatory gut microbial metabolite of dietary tryptophan (Figure 2). There was also a positive correlation between Bifidobacterium and IL10, a major anti-inflammatory cytokine that plays a role in cardiac remodeling. Conclusion: Bifidobacterium was independently associated with longitudinal improvement in functional status in patients with HFrEF. Additionally, Bifidobacterium correlated with circulating IPA, malonic acid, and IL10. Our findings support (1) gut Bifidobacterium as a potential biomarker of clinical improvement in HFrEF and a possible new therapeutic target, and (2) potential downstream mediators through which Bifidobacterium may regulate HF pathophysiology.