Concentration Values Research Articles

Nisin-loaded chitosan/sodium alginate microspheres enhance the antimicrobial efficacy of nisin against Staphylococcus aureus.

To develop and evaluate nisin-loaded chitosan/sodium alginate (CS/SA) microspheres as an improved antimicrobial delivery system targeting Staphylococcus aureus strains. The microspheres were prepared using a modified water-in-oil emulsion cross-linking method, resulting in spherical particles sized 1-8µm with a surface charge of -7.92±5.09mV, confirmed by scanning electron microscopy (SEM) and Zetasizer analysis. Encapsulation efficiency (EE) and loading capacity (LC) of nisin were 87.60±0.43% and 1.99±0.01%, respectively. In vitro release studies over 48 hours indicated a controlled release pattern of nisin, described by the Korsmeyer-Peppas model, with higher release rates at 37°C and alkaline pH. Antimicrobial assays showed an enhanced efficacy of nisin-loaded CS/SA microspheres compared to free nisin, with minimum inhibitory concentration (MIC) values reduced by 50%. Confocal laser scanning microscopy (CLSM), SEM and transmission electron microscopy (TEM) showed significant bacterial membrane damage and cellular disruption induced by the microspheres. This study highlights the potential of nisin-loaded CS/SA microspheres as an innovative antimicrobial delivery system with improved stability and antimicrobial efficacy against S. aureus, addressing limitations associated with nisin alone.

An Accurate and Fast 31P qNMR Assay Method for Oligonucleotide Therapeutics.

Chemically modified nucleic acid molecules have been developed as oligonucleotide therapeutics, and its assay is critical in quality assurance. The common DNA/RNA quantification method using UV-260 nm can lack accuracy because of structure modifications and the possible formation of higher-order structure (HOS). Additionally, process-associated water and counterions affect the accuracy in gravimetric analysis. Thus, to improve accuracy, efficiency, and flexibility, in this work a fast (<1 h) externally referenced 31P quantitative-NMR (qNMR) method was developed. The qNMR assay results agreed within 1-5% of the UV-260 nm results for the single-stranded DNA standards, confirming the method accuracy. Next, an NMR and UV comparison study was performed on intact oligonucleotide drug products. The 31P qNMR method showed 7 ± 2%, 8 ± 1%, and 12 ± 1% lower concentration values compared with drug product labels for eteplirsen, inotersen, and inclisiran, respectively. Meanwhile the UV-260 nm results showed 28 ± 3%, 10 ± 3%, and 10 ± 1% lower concentrations than the label for the same three drugs. The agreement between NMR and UV for phosphorothioate (PS)-based inotersen and mostly phosphodiester (PO)-based inclisiran suggest that the labeled concentration may have been obtained using different extinction coefficients. The underestimate of UV results for eteplirsen, which has a phosphorodiamidate morpholino oligomer (PMO) structure, suggests that the UV-260 nm extinction coefficient may need to be re-established for the PMO based oligonucleotide. Therefore, the 31P qNMR method could be a primary assay method for the oligonucleotide drug and reference standard.

Assessment of solitary pulmonary nodules using dual-layer spectral detector computed tomography.

We aim to quantitatively investigate the difference between benign and malignant solid pulmonary nodules that appeared on dual-energy spectral computed tomography, and assess the diagnostic accuracy of several parameters derived from computed tomography in differentiating malignant from benign pulmonary nodules. Between September 2021 and December 2022, spectral images of 71 patients (male:female = 44:27, mean age = 71.0 years) confirmed by pathology were retrospectively analyzed in the venous phase. Patients were classified into the malignant group and the benign group. The iodine concentration values of the nodules, normalized iodine concentration of the nodules to the neighboring vessels, virtual monochromatic images of 40 and 80 keV, and slope of the spectral curve were calculated and compared between the benign and malignant groups. Receiver operating characteristic curves and the area under the curve were performed to assess the diagnostic performance of the above parameters. Both virtual monochromatic images and iodine concentration maps prove to be highly useful in differentiating benign and malignant pulmonary nodules. The malignant pulmonary nodules have higher iodine density and slope of the spectral curve than the benign lesions. The combined model of iodine density and curve slope with an optimal cutoff of 0.39 (area under the curve = 0.82) yielded a sensitivity of 95% and a specificity of 63%. Contrast-enhanced dual-energy spectral computed tomography allows promising capability of distinguishing malignant from benign lesions, potential for avoiding unnecessary invasive procedure or surgery.

Unveiling the Behavior of an Endangered Facultative Cuprophyte Coincya Species in an Abandoned Copper Mine (Southeast Portugal).

Plant-soil interactions of endangered species with a high-priority conservation status are important to define in situ and ex situ conservation and restoration projects. The threatened endemic Coincya transtagana, thriving in the southwest of the Iberian Peninsula, can grow in metalliferous soils. The main goal of this study was to investigate the behavior of this species in soils rich in potentially toxic elements in the abandoned Aparis Cu mine. Soil samples were characterized for physicochemical properties and multielemental composition, as well as biological activity, through an analysis of enzymatic activities. Plant biomass was assessed, and multielemental analysis of the plants was also performed. The mine soils had slightly basic pH values and were non-saline and poor in mineral N-NH4, with medium-to-high organic matter concentration and medium cation-exchange capacity. In these soils, dehydrogenase had the highest activity, whereas protease had the lowest activity. The total concentrations of Cu (1.3-5.9 g/kg) and As (37.9-118 mg/kg) in soils were very high, and the available fraction of Cu in the soil also had high concentration values (49-491 mg/kg). Moreover, this study shows for the first time that C. transtagana had high uptake and translocation capacities from roots to shoots for Cu, Ni, and Cr. Although Cu in the plants' aerial parts (40-286 mg/kg) was considered excessive/toxic, no signs of plant toxicity disorders or P uptake reduction were detected. This preliminary study revealed that C. transtagana is Cu-tolerant, and it could be used for phytoremediation of soils contaminated with potentially toxic elements, while also contributing to its conservation.

Scientific substantiation of the maximum permissible concentration of the pharmaceutical substance osimertinib mesylate in the air of the working area

Introduction. Osimertinib, a 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor, is currently the only drug registered for the treatment of metastatic non-small cell lung cancer in patients with a positive T790M mutation status. The production of osimertinib mesylate is planned on the territory of the Russian Federation, which necessitates research to substantiate the hygienic standard for the aerosol content of the substance in the air of the working area. Conducting research to substantiate the maximum permissible concentration of a substance requires significant material and time resources, while using the results of preclinical and clinical studies, mathematical modeling of processes, and risk assessment methodology allows for a comprehensive assessment of the substance, while significantly reducing the time and cost of work. The study aims to scientifically substantiate the maximum permissible concentration of the pharmaceutical substance osimertinib mesylate in the air of the working area using data from toxicological studies and mathematical modeling of the effects of the substance on humans in industrial conditions. Materials and methods. The materials used were domestic and international databases, reports, research protocols, scientific articles and monographs containing information on the physico-chemical and toxic properties, pharmacotherapeutic activity of osimertinib. Results. The specialists have conducted hygienic regulation of osimertinib, taking into account data on its toxicity, danger, pharmacotherapeutic activity, side effects, long-term consequences, pharmacokinetic studies and modeling. To substantiate the value of the maximum permissible concentration, the authors used the reference points: an inactive NOEL level of 1 mg/­kg/­day for general toxic effect, established in a 92-day experiment on rats with intragastric administration; the lowest observed level of adverse effects of LOAEL is 0.5 mg/kg/day for general toxic effect, established in a 180-day experiment on dogs with intragastric administration; the level that does not cause adverse effects of NOAEL is 10 mg/kg/day for general toxic effect, established in a 180-day experiment on mice with intragastric administration. Safe concentrations of osimertinib in the air of the work area were evaluated using reference points, including the pharmacological effect and the minimum daily therapeutic dose; toxicokinetic modeling of concentrations of a substance in the human body under production conditions and the level of minimal risk. Limitation. The study is limited to the review of open literature sources describing the toxicological/toxicokinetic characteristics of osimertinib mesylate. Conclusion. The most stringent indicators of safe exposure levels, established on the basis of pharmacological effect and toxicokinetic modeling in dogs, allowed us to recommend 0.005 mg/m3, aerosol, hazard class 1 as the maximum permissible concentration in the air of the working area for osimertinib mesylate. Ethics. This study did not require the conclusion of the Ethics Committee.

Quercetin: Potential antidiabetic effects through enzyme inhibition and starch digestibility

AbstractDiabetes mellitus involves high blood sugar levels due to insufficient insulin action. Furthermore, enzymes such as α‐amylase and α‐glucosidase break down carbohydrates into glucose, leading to postprandial hyperglycemia. Flavonoids, particularly quercetin, inhibit these enzymes, slowing carbohydrate digestion and reducing glucose absorption. Quercetin has significant hypoglycemic effects with inhibitory concentration (IC50) values comparable to acarbose, a standard inhibitor, suggesting its potential as a natural alternative for diabetes management. In silico models, including molecular docking, molecular dynamics (MD) simulations, and quantitative structure‐activity relationship (QSAR) approaches, help researchers understand the molecular interactions of therapeutic agents. These techniques identify potential inhibitors, determine enzyme‐inhibitor structures, and calculate binding energies, correlating findings with in vitro or in vivo data. Molecular docking predicts molecular orientations, MD simulations offer insights into enzyme–inhibitor dynamics, and QSAR models predict inhibitory potential based on structural properties. Studies have shown that quercetin effectively inhibits α‐glucosidase and α‐amylase by forming hydrogen bonds with specific amino acid residues. Quercetin interacts with starches and reduces their digestibility, increases the formation of resistant starch, lowers the glycemic index, and inhibits digestive enzymes. Studies show that the effects of quercetin on starch digestion vary with concentration and type of starch, and its incorporation into foods such as bakery products, pasta, etc. can significantly decrease starch hydrolysis. The incorporation of quercetin into starch matrices may aid in the development of functional foods aimed at improving glycemic control.

Influence of Emulsion Lipid Droplet Crystallinity on Postprandial Endotoxin Transporters and Atherogenic And Inflammatory Profiles in Healthy Men - A Randomized Double-Blind Crossover Acute Meal Study.

Consumption of high-fat meals is associated with increased endotoxemia, inflammation, and atherogenic profiles, with repeated postprandial responses suggested as contributors to chronically elevated risk factors. However, effects of lipid solid versus liquid state specifically have not been investigated. This exploratory randomized crossover study tests the impact of lipid crystallinity on plasma levels of endotoxin transporters (lipopolysaccharide [LPS] binding protein [LBP] and soluble cluster of differentiation 14 [sCD14]) and select proinflammatory and atherogenic markers (tumor necrosis factor-alpha [TNF-α], C-reactive protein [CRP], interleukin-1-beta [IL-1β], interferon-gamma [IFN-γ], interleukin-6 [IL-6], soluble intercellular adhesion molecule [sICAM], soluble vascular cell adhesion molecule [sVCAM], monocyte chemoattractant protein-1 [MCP-1/CCL2], plasminogen activator inhibitor-1 [PAI-1], and fibrinogen). Fasted healthy men (n = 14, 28 ± 5.5 years, 24.1 ± 2.6kgm-2) consumed two 50g palm stearin oil-in-water emulsions tempered to contain either liquid or crystalline lipid droplets at 37°C on separate occasions with blood sampling at 0, 2-, 4-, and 6-h post-meal. Timepoint data, area under the curve, and peak concentration values are compared. Overall, no treatment effects are seen (p > 0.05). There are significant effects of time, with values decreasing from baseline, for TNF-α, MCP-1/CCL2, PAI-1, and fibrinogen (p < 0.05). Responder analysis pointed to differential treatment effects associated with some participant baseline characteristics but, overall, palm-stearin emulsion droplet crystallinity does not acutely affect plasma endotoxin transporters nor select inflammatory and atherogenic markers.

Unraveling the Formation of Ternary AgCuSe Crystalline Nanophases and Their Potential as Antibacterial Agents.

AgCuSe nanoparticles could contribute to the growth of strongly light-absorbing thin films and solids with fast ion mobility, among other potential properties. Nevertheless, few methods have been developed so far for the synthesis of AgCuSe nanoparticles, and those reported deliver nanostructures with relatively large sizes and broad size and shape distributions. In this work, a colloidal cation exchange method is established for the easy synthesis of AgCuSe NPs with ca. 8 nm diameters and narrow size dispersion. Notably, in this lower size range the conucleation and growth of two stoichiometric ternary compounds are generally observed, namely the well-known eucairite AgCuSe compound and the novel fischesserite-like Ag3CuSe2 phase, the latter being less thermodynamically stable as predicted computationally and assessed experimentally. An optimal range of Cu/Ag precursor molar ratio has been identified to ensure the growth of ternary nanoparticles and, more specifically, that of the metastable Ag3CuSe2 nanophase isolated for the first occasion. The attained size range for the material paves the way for utilizing AgCuSe nanoparticles in new ways within the field of biomedicine: the results obtained here confirm the antibacterial activity of the new Ag x Cu y Se z nanoparticles against Gram-positive bacteria, with significantly low values of the minimal inhibitory concentration.

Aggregation behavior, interaction forces and physico-chemical parameters of cetyltrimethylammonium chloride in aqueous solution of bovine serum albumin: Impacts of short-chain alcohols and temperature

To better understand the molecular interactions between cetyltrimethylammonium chloride (CTAC) and bovine serum albumin (BSA), we report the alteration of the physicochemical characteristics of CTAC in aqueous BSA solutions in the presence of different alcohols. The analyses were performed using the conductivity method at temperatures ranging from 298.15 to 323.15 K, with 5 K intervals. The critical micelle concentration (CMC) values of the BSA + CTAC systems were found to change with variations in alcohol types, solvent compositions, and temperatures. The CMC values grew with the rising of alcohol contents. The negative free energy changes (∆Gm0) indicated the spontaneous association of the systems in all solvents media. The magnitudes of ∆Hm0 and ∆Sm0, determined from the micellization of the systems, indicated the presence of electrostatic, ion-dipole, and hydrophobic forces. The thermodynamics of transfer (free energy (∆Gm,tr0), enthalpy (∆Hm,tr0), entropy (∆Sm,tr0)), and compensation parameters (∆Hm0,∗ and Tc)—were also calculated, which provided significant insights into the potential interactions between CTAC and BSA in the presence of various alcohol additives. Furthermore, molecular docking studies suggested the binding of CTAC to different BSA binding sites with varying affinities.

WO3@MOF heterostructure in-situ transformed and deposited on La-Bi2WO6-BiFeWOx composite with enhanced photocatalytic performance for degradation of harmful and toxic substances produced by tobacco

Nowadays, tobacco is widely cultivated, and there are millions of people who smoke around the world. The cultivation of tobacco, along with the handling of cigarettes and the consumption of tobacco products, can produce numerous harmful and toxic substances. Many researchers are working diligently to eliminate these harmful and toxic substances. However, the results have been minimal. In this paper, we successfully prepared a novel La-Bi2WO6-BiFeWOx-WO3@MOF using hydrothermal and in-situ transformation methods. All samples were thoroughly investigated using various characterization techniques, including XRD, SEM, TEM, XPS, UV–Vis absorption spectra, transient photocurrent responses, and electron spin resonance. Furthermore, La-Bi2WO6-BiFeWOx-WO3@MOF was utilized as a catalyst for the degradation of harmful and toxic substances produced by tobacco, including phenol, nicotine, benzopyrene, and nitrosamines. The results indicate that La-Bi2WO6-BiFeWOx-WO3@MOF exhibits efficient separation and transfer of photo-generated electron-hole pairs under visible light irradiation. La-Bi2WO6-BiFeWOx-WO3@MOF also exhibits excellent photocatalytic activity, efficiently degrading phenol (98.62%), nicotine (92.41%), benzopyrene (81.74%), and nitrosamine (98.23%). Furthermore, the effects of varying catalyst dosage, phenol concentration, and pH values, as well as the degradation of nicotine, benzopyrene, and nitrosamine by La-Bi2WO6-BiFeWOx-WO3@MOF, were also investigated. The main active radicals are ·OH and ·O2– during the degradation process. Finally, a potential degradation mechanism for phenol, nicotine, benzopyrene, and nitrosamine by La-Bi2WO6-BiFeWOx-WO3@MOF is proposed.

Assessment of the activity and mechanisms of resistance to cefiderocol and combinations of β-lactams and the novel β-lactamase inhibitors avibactam, taniborbactam, zidebactam, nacubactam, xeruborbactam, and ANT3310 in emerging double-carbapenemase-producing Enterobacterales.

We aimed to investigate the activity of and mechanisms of resistance to cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations in a nationwide collection of double-carbapenemase-producing Enterobacterales. In all, 57 clinical isolates co-producing two carbapenemases collected from Spanish hospitals during the period 2017-2022 were analyzed. Minimum inhibitory concentration (MIC) values for ceftazidime, ceftazidime/avibactam, aztreonam, aztreonam/avibactam, aztreonam/nacubactam, cefiderocol, cefepime, cefepime/taniborbactam, cefepime/zidebactam, cefepime/nacubactam, imipenem, imipenem/relebactam, meropenem, meropenem/vaborbactam, meropenem/xeruborbactam, and meropenem/ANT3310 were determined by reference broth microdilution. Genetic drivers of resistance were analyzed by whole-genome sequencing (WGS). The collection covered nine carbapenemase associations: VIM + OXA-48 (21/57), NDM + OXA-48 (11/57), KPC + VIM (10/57), KPC + OXA-48 (6/57), IMP + OXA-48 (3/57), NDM + KPC (2/57), NDM + VIM (2/57), NDM + GES (1/57), and KPC + IMP (1/57). Ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam were the least active options. Aztreonam/avibactam and aztreonam/nacubactam were active against the whole collection and yielded MIC50/MIC90 values of ≤0.25/0.5 mg/L and 1/2 mg/L, respectively. Cefepime/zidebactam (56/57 susceptible), meropenem/xeruborbactam (56/57 susceptible), cefepime/nacubactam (55/57 susceptible), and cefiderocol (53/57 susceptible) were also highly active, with MIC50/MIC90 values ranging from ≤0.25-2 mg/L to 2-4 mg/L, respectively. Meropenem/ANT3310 (MIC50/MIC90 = 0.5/≥64 mg/L; 47/57 susceptible) and cefepime/taniborbactam (MIC50/MIC90 = 0.5/16 mg/L; 44/57 susceptible) also retained high levels of activity, although they were affected by NDM-type enzymes in combination with porin deficiency. Our findings highlight that cefiderocol and combinations of β-lactams and the novel β-lactamase inhibitors avibactam, nacubactam, taniborbactam, zidebactam, xeruborbactam, and ANT3310 show promising activity against double-carbapenemase-producing Enterobacterales.

Effect of solvent polarity on yield extract, antioxidant and antibacterial activities of phytochemicals from Andrographis paniculata leaves

ABSTRACT In this study, the impact of solvent polarity on the extraction yield, antibacterial activity and antioxidant characteristics of phytochemical compounds derived from Andrographis paniculata leaves was investigated. The simplicia of A. paniculata was macerated in different organic solvents with raising polarity (n-Hexane, ethyl acetate, dichloromethane, ethanol, methanol, methanol–water) at room temperature for 24 h. Preliminary screening revealed that the yield extract, phytochemical composition, antibacterial activity and antioxidant properties were influenced by the polarity of the solvent used for extraction. The optimum yield extract was obtained using a methanol–water solvent (50:50, v/v) of 15.46%. The most active antibacterial activity against biofilm-forming bacteria (Pseudomonas aeruginosa) was obtained using ethyl acetate and dichloromethane with a minimum inhibition concentration (MIC) value of 312.5 µg mL−1. Meanwhile, the antioxidant properties of A. paniculata leaf extract with all solvents shows a very weak level. The antibacterial activity and antioxidant properties of A. paniculata leaf extracts are related to the phytochemical content in the extract. This result is evident in the extract with ethyl acetate solvents with the highest total phenolic and flavonoid values. However, GC-MS analysis of A. paniculata extract revealed 20 components, with Supraene having the greatest compounds.

Risk assessment and quantification of elemental concentrations in river and stream in Nigeria

The rising prevalence of elements in surface water is becoming a major global environmental problem due to their resistance to change and capacity to accumulate in organisms. Humans are causing significant heavy metal contamination in the aquatic environment, which is killing aquatic creatures. The purpose of this study is to determine the elemental composition of surface water in Ogun State. Water samples were collected from a river that flows alongside Liberty Estate in Ewupe, Ado-Odo Ota Local Government Area, and a stream that runs alongside Pacific Estate in Iganmode. The element composition of water samples was determined using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Several components were found to exceed the limitations imposed by the World Health Organisation (WHO) and the Environmental Protection Agency (EPA). In River I, sodium (Na) had the highest apparent concentration, whereas titanium (Ti) had the lowest average concentration. In River II, silicon (Si) had the highest apparent concentration, whereas chromium (Cr) had the lowest average concentration. Titanium (Ti) had the lowest mean concentration value, whereas sodium (Na) appeared to have the highest concentration in stream I. Stream II has the highest concentration of sodium (Na), while Uranium (U) has the lowest average concentration value. Nonetheless, the incremental lifetime cancer risk (ILCR) values for adults and children who drink river and stream water are similar, ranging from 10–9 to 10–8. This implies a high carcinogenic risk (CR) linked with drinking water from both sources. Children who had access to both stream and river water demonstrated higher risk levels than adults. Routine studies of the state's streams and rivers should be conducted to avoid the subtle impact that may emanate from the water bodies.

Quantitative brain T1 maps derived from T1-weighted MRI acquisitions: a proof-of-concept study.

Longitudinal T1 relaxation time is a key imaging biomarker. In addition, T1 values are modulated by the administration of T1 contrast agents used in patients with tumors and metastases. However, in clinical practice, dedicated T1 mapping sequences are often not included in brain MRI protocols. The aim of this study is to address the absence of dedicated T1 mapping sequences in imaging protocol by deriving T1 maps from standard T1-weighted sequences. A phantom, composed of 144 solutions of paramagnetic agents at different concentrations, was imaged with a three-dimensional (3D) T1-weighed turbo spin-echo (TSE) sequence designed for brain imaging. The relationship between the T1 values and the signal intensities was established using this phantom acquisition. T1 mapping derived from 3D T1-weighted TSE acquisitions in four healthy volunteers and one patient with brain metastases were established and compared to reference T1 mapping technique. The concentration of Gd-based contrast agents in brain metastases were assessed from the derived T1 maps. Based on the phantom acquisition, the relationship between T1 values and signal intensity (SI) was found equal to T1 = 0.35 × SI-1.11 (R2 = 0.97). TSE-derived T1 values measured in white matter and gray matter in healthy volunteers were equal to 0.997 ± 0.096 s and 1.358 ± 0.056 s (mean ± standard deviation), respectively. Mean Gd3+ concentration value in brain metastases was 94.7 ± 30.0 μM. The in vivo results support the relevance of the phantom-based approach: brain T1 maps can be derived from T1-weighted acquisitions. High-resolution brain T1 maps can be generated, and contrast agent concentration can be quantified and imaged in brain metastases using routine 3D T1-weighted TSE acquisitions. Quantitative T1 mapping adds significant value to MRI diagnostics. T1 measurement sequences are rarely included in routine protocols. T1 mapping and concentration of contrast agents can be derived from routine standard scans. The diagnostic value of MRI can be improved without additional scan time.

Onametostat, a PfPRMT5 inhibitor, exhibits antimalarial activity to Plasmodium falciparum.

Protein arginine methyltransferases (PRMTs) play critical roles in Plasmodium falciparum, a protozoan causing the deadliest form of malaria, making them potential targets for novel antimalarial drugs. Here, we screened 11 novel PRMT inhibitors against P. falciparum asexual growth and found that onametostat, an inhibitor for type II PRMTs, exhibited strong antimalarial activity with a half-maximal inhibitory concentration (IC50) value of 1.69 ± 0.04 µM. In vitro methyltransferase activities of purified PfPRMT5 were inhibited by onametostat, and a shift of IC50 to onametostat was found in the PfPRTM5 disruptant parasite line, indicating that PfPRTM5 is the primary target of onametostat. Consistent with the function of PfPRMT5 in mediating symmetric dimethylation of histone H3R2 (H3R2me2s) and in regulating invasion-related genes, onametostat treatment led to the reduction of H3R2me2s level in P. falciparum and caused the defects on the parasite's invasion of red blood cells. This study provides a starting point for identifying specific PRMT inhibitors with the potential to serve as novel antimalarial drugs.

Recent increase in Candida auris frequency in the SENTRY surveillance program: antifungal activity and genotypic characterization.

We observed an increase in the frequency of Candida auris among invasive candidiasis isolates in the 2022 SENTRY Antifungal Surveillance Program compared to prior years: ≤0.1% before 2018, 0.4%-0.6% from 2018 to 2021, and 1.6% in 2022. C. auris isolates were collected in seven countries, but 28 (35.9%) isolates were recovered in the USA (five states; more common in New York, Texas, and New Jersey) and 26 (33.3%) in Panama. Greece and Turkey had 12 and 9 isolates, respectively. Overall, 82.1% of the isolates were resistant to fluconazole; 17.9% were resistant to amphotericin B; and 1.3% were resistant to caspofungin, anidulafungin, or micafungin (Centers for Disease Control and Prevention tentative resistance breakpoints). Rezafungin inhibited 96.2% of the isolates (Clinical and Laboratory Standards Institute susceptibility breakpoint). Pandrug resistance was not observed, but 17.9% of the isolates were resistant to fluconazole and amphotericin B. South Asian (Clade I) isolates were most common (n = 40, 51.3%); of these, 97.5% were resistant to fluconazole and 30.0% were resistant to amphotericin B. Thirty (38.5%) isolates belonged to the South American region (Clade IV), and 56.7% of those were resistant to fluconazole and 6.7% to amphotericin B. Seven isolates belonged to the South African Clade III and one to East Asian Clade II. Erg11 (Y132F, K143R, and F126L) and MRR1 (N647T) alterations were detected. One isolate that was resistant to all echinocandins carried an FKS R1354G alteration. Two isolates displayed elevated rezafungin minimum inhibitory concentration (MIC) values but low MIC values against other echinocandins and no FKS alterations. As C. auris is spreading globally, monitoring this species is prudent.

Automated calculation and reporting of vancomycin area under the concentration-time curve: a simplified single-trough concentration-based equation approach.

Vancomycin, a crucial antibiotic for Gram-positive bacterial infections, requires therapeutic drug monitoring (TDM). Contemporary guidelines advocate for AUC-based monitoring; however, using Bayesian programs for AUC estimation poses challenges. We aimed to develop and evaluate a simplified AUC estimation equation using a steady-state trough concentration (Ctrough) value. Utilizing 1,034 TDM records from 580 general hospitalized patients at a university-affiliated hospital in Ulsan, we created an equation named SSTA that calculates the AUC by applying Ctrough, body weight, and single dose as input variables. External validation included 326 records from 163 patients at a university-affiliated hospital in Seoul (EWUSH) and literature data from 20 patients at a university-affiliated hospital in Bangkok (MUSI). It was compared with other AUC estimation models based on the Ctrough, including a linear regression model (LR), a sophisticated model based on the first-order equation (VancoPK), and a Bayesian model (BSCt). Evaluation metrics, such as median absolute percentage error (MdAPE) and the percentage of observations within ±20% error (P20), were calculated. External validation using the EWUSH data set showed that SSTA, LR, VancoPK, and BSCt had MdAPE values of 6.4, 10.1, 6.6, and 7.5% and P20 values of 87.1, 82.5, 87.7, and 83.4%, respectively. External validation using the MUSI data set showed that SSTA, LR, and VancoPK had MdAPEs of 5.2, 9.4, and 7.2%, and P20 of 95, 90, and 95%, respectively. Owing to its decent AUC prediction performance, simplicity, and convenience for automated calculation and reporting, SSTA could be used as an adjunctive tool for the AUC-based TDM.

The chemical composition, antioxidative and antimicrobial potentials of Toona sinensis essential oils from different regions of China

Toona sinensis is one of the traditional Chinese medicinal materials with rich physiological activities. This study aimed to investigate the chemical composition differences of the essential oils from the tender leaves and shoots of T. sinensis, collected from four main producing areas in China, and to verify their anti-listeria and antioxidant properties. Gas chromatography-mass spectrometry (GC-MS) analysis was conducted on the essential oils obtained by hydro-distillation. The results indicated that compounds such as β-elemene (3.5∼8.1%), α-caryophyllene (3.7∼7.2%), and trans-caryophyllene (4.0∼9.7%) were the main common components of T. sinensis essential oils (TSEO) from four producing areas. The results of DPPH and ABTS showed that the essential oil from Dazhou, Sichuan, China had the best antioxidant effect. At a concentration of 1.25 mg/mL, the antioxidant activity of TSEO-DZ from Sichuan was comparable to 0.08 mg/mL of BHT and was only slightly lower than 0.06 mg/mL of VC. The broth dilution method showed that the essential oil from Tai ‘an, Shandong, China, showed better antibacterial effect, with the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MLC) values of 1.25 μL/mL and 2.54 μL/mL, respectively. This study demonstrates that TSEO possesses promising application potential in antioxidant and anti-listeria activities, and it confirms that the growth environment of T. sinensis significantly influences the quality, content, and biological activity of the essential oil.

Tyrosinase Inhibitory Activity of Crude Procyanidin Extract from Green Soybean Seed and the Stability of Bioactive Compounds in an Anti-Aging Skin Care Formulation

Green soybean (Glycine max L.) seed contains a high procyanidin content and high antioxidant activity. Moreover, ultrasound-assisted extraction (UAE) has proved to be advantageous in providing high extraction efficiency. Hence, this study aimed to extract procyanidins from green soybean seeds (GSSs) using UAE. This study also evaluated the inhibitory activities of tyrosinase and the cytotoxic effects of crude procyanidin extract. The extract exhibited maximum levels of bioactive components and antioxidant capacity when subjected to a temperature of 15 °C and an extraction time of 20 min. The crude procyanidin extract at a concentration of 10 mg/mL inhibited the tyrosinase enzyme by more than 60%, and the half-maximal inhibitory concentration (IC50) value obtained for the extract was 6.85 ± 0.81 mg/mL. This result was much greater than the IC50 value obtained for kojic acid (0.089 ± 0.08 mg/mL), which was used as a positive control. For the cytotoxicity assessment, the results indicated that the crude procyanidin extract showed no cytotoxicity and actually stimulated the growth of human skin fibroblast cells. More than 80% of the bioactive compounds (total phenolic content (TPC), total flavonoid content (TFC), procyanidin content (PC)) and antioxidant activities (DPPH and FRAP) of the crude extract powder were retained at 38.68 ± 0.01 mg GAE/g, 16.07 ± 0.01 mg CAE/g, 9.24 ± 0.01 mg PC/g, 359.8 ± 0.72 μM Trolox eq/g, and 1640 ± 2.86 μM Trolox eq/g, respectively, after 12 weeks of storage at 25 °C. The crude procyanidin extract powder was then included in a facial serum formulation and tested for pH value and physical evaluation. The stability of the crude procyanidin extract facial serum was shown to be greater for bioactive compounds and antioxidant activity when stored at a temperature of 4 °C than when stored at a temperature of 25 °C. These results suggest that the GSS extracts obtained via ultrasonication show promise for use in cosmeceutical formulations for whitening skincare products.

Innovative Microencapsulation of Polymyxin B for Enhanced Antimicrobial Efficacy via Coated Spray Drying.

This study aims to develop an innovative microencapsulation method for coated Polymyxin B, utilizing various polysaccharides such as hydroxypropyl β-cyclodextrin, alginate, and chitosan, implemented through a three-fluid nozzle (3FN) spray drying process. High-performance liquid chromatography (HPLC) analysis revealed that formulations with a high ratio of sugar cage, hydroxypropyl β-cyclodextrin (HPβCD), and sodium alginate (coded as ALGHCDHPLPM) resulted in a notable 16-fold increase in Polymyxin B recovery compared to chitosan microparticles. Morphological assessments using fluorescence labeling confirmed successful microparticle formation with core/shell structures. Alginate-based formulations exhibited distinct layers, while chitosan formulations showed uniform fluorescence throughout the microparticles. Focused beam reflectance and histograms from fluorescence microscopic measurements provided insights into physical size analysis, indicating consistent sizes of 6.8 ± 1.2 μm. Fourier-transform infrared (FTIR) spectra unveiled hydrogen bonding between Polymyxin B and other components within the microparticle structures. The drug release study showed sodium alginate's sustained release capability, reaching 26 ± 3% compared to 94 ± 3% from the free solution at the 24 h time point. Furthermore, the antimicrobial properties of the prepared microparticles against two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, were investigated. The influence of various key excipients on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values was evaluated. Results demonstrated effective bactericidal effects of ALGHCDHPLPM against both E. coli and P. aeruginosa. Additionally, the antibiofilm assay highlighted the potential efficacy of ALGHCDHPLPM against the biofilm viability of E. coli and P. aeruginosa, with concentrations ranging from 3.9 to 500 μg/m. This signifies a significant advancement in antimicrobial drug delivery systems, promising improved precision and efficacy in combating bacterial infections.