Native Compound Research Articles

Substrate Specificity of a Methyltransferase Involved in the Biosynthesis of the Lantibiotic Cacaoidin.

Modification of the N- and C-termini of peptides enhances their stability against degradation by exopeptidases. The biosynthetic pathways of many peptidic natural products feature enzymatic modification of their termini, and these enzymes may represent a valuable pool of biocatalysts. The lantibiotic cacaoidin carries an N,N-dimethylated N-terminal amine group. Its biosynthetic gene cluster encodes the putative methyltransferase Cao4. In this work, we present reconstitution of the activity of the enzyme, which we termed CaoSC following standardized lanthipeptide nomenclature, using a heterologously produced peptide as the model substrate. In vitro methylation of diverse lanthipeptides revealed the substrate requirements of CaoSC. The enzyme accepts peptides of varying lengths and C-terminal sequences but requires dehydroalanine or dehydrobutyrine at the second position. CaoSC-mediated dimethylation of natural lantibiotics resulted in modestly enhanced antimicrobial activity of the lantibiotic haloduracin compared to that of the native compound. Improved activity and/or metabolic stability as a result of methylation illustrates the potential future application of CaoSC in the bioengineering of therapeutic peptides.

In Vitro Studies of Genistein Lipophilic Derivatives as Potential UV Radiation Protectors.

The major environmental factor responsible for skin cancer is ultraviolet (UV) radiation, present in sunlight. UV radiation is directly linked to the production of reactive oxygen species (ROS), which accumulate in exposed cells and cause serious damage. The antioxidant systems present in cells cannot always sufficiently neutralize the ROS. Therefore, supplementation with exogenous antioxidants has been proposed. The antioxidant properties of some isoflavones, such as genistein, have already been well-proven. Genistein has limited bioavailability. However, its derivatives, with increased lipophilicity, could facilitate its transfer into cells, where they can expose its antioxidative potential. This study aims to investigate three genistein derivatives, with greater lipophilicity than the native compound, regarding their cytotoxicity, antioxidative properties, and effect on the cell cycle in normal human dermal fibroblasts (NHDF) and a melanoma cancer cell line (Me45). Results showed that lipophilic modification of the genistein molecule changes the biological response of NHDF and Me45 cell lines to UV-C radiation, but the lipophilicity cannot be directly linked with the activity of the compounds. A comparison of the effects of the genistein derivatives on healthy and cancerous cells suggests that their mode of action strongly depends on the type of cell involved.

In Situ Eutectic Formation in a Polymeric Matrix via Hot-Melt Reactive Extrusion and the Use of Partial Least Squares Regression Modeling for Reaction Yield Determination.

There has been a significant volume of work investigating the design and synthesis of new crystalline multicomponent systems via examining complementary functional groups that can reliably interact through the formation of noncovalent bonds, such as hydrogen bonds (H-bonds). Crystalline multicomponent molecular adducts formed using this approach, such as cocrystals, salts, and eutectics, have emerged as drug product intermediates that can lead to effective drug property modifications. Recent advancement in the production for these multicomponent molecular adducts has moved from batch techniques that rely upon intensive solvent use to those that are solvent-free, continuous, and industry-ready, such as reactive extrusion. In this study, a novel eutectic system was found when processing albendazole and maleic acid at a 1:2 molar ratio and successfully prepared using mechanochemical methods including liquid-assisted grinding and hot-melt reactive extrusion. The produced eutectic was characterized to exhibit a 100 °C reduction in melting temperature and enhanced dissolution performance (>12-fold increase at 2 h point), when compared to the native drug compound. To remove handling of the eutectic as a formulation intermediate, an end-to-end continuous-manufacturing-ready process enables feeding of the raw parent reagents in their respective natural forms along with a chosen polymeric excipient, Eudragit EPO. The formation of the eutectic was confirmed to have taken place in situ in the presence of the polymer, with the reaction yield determined using a multivariate calibration model constructed by combining spectroscopic analysis with partial least-squares regression modeling. The ternary extrudates exhibited a dissolution profile similar to that of the 1:2 prepared eutectic, suggesting a physical distribution (or suspension) of the in situ synthesized eutectic contents within the polymeric matrix.

Linguistic synesthesia in language contact: Sino-Korean vs. native Korean synesthetic compounds

This study examines whether linguistic synesthesia shares mapping directionality across languages and cultures in terms of language contact. This motivation has led to the examination of Sino-Korean synesthetic compounds compared to native Korean ones. A comparative analysis of Sino-Korean and native Korean synesthesia proposes that language contact has observed linguistic variations in transfer directionality in linguistic synesthesia. In other words, this study’s results show that Sino-Korean compound synesthesia has a directionality model similar to Mandarin Chinese, which differs from previous universality models. In contrast, native Korean compound synesthesia directionality follows diagrams from Korean synesthesia research and previous studies based on Indo-European languages.

P-225 Implementing a more physiological method to trigger oocyte activation in cases of extremely poor fertilization with ICSI

Abstract Study question Can we utilize a more physiological compound to induce oocyte activation in couples with history of complete/partial fertilization failure with ICSI? Summary answer Recombinant human phospholipase-C-zeta (rhPLCζ) successfully activated oocytes with same efficiency as ionomycin, consistently normalized fertilization and enhanced clinical outcomes. What is known already While ICSI overcomes most aspects of male gamete dysfunction, partial or complete fertilization failure may seldomly occur mostly due absence of sperm-specific protein, known as PLCζ, which is required to trigger oocyte activation. Assisted oocyte activation (AOA), most often performed with an antibiotic (ionomycin), activates oocytes by triggering calcium release from intracellular storage. This agent induces indiscriminate permeabilization of ooplasmic membrane-bound organelles. This action has been considered nonspecific and may have possible deleterious effects on subsequent embryo development. Therefore, we propose a physiological alternative that employs a recombinant form of PLCζ, the native protein residing in the sperm perinuclear theca. Study design, size, duration In the past 12 months, couples with poor ICSI fertilization were included. PLCζ were assessed to confirm sperm-related oocyte activation deficiency with a normal threshold of ≥ 30%. In a preliminary comparison, sibling oocytes were equally allocated to AOA by ionomycin or to rhPLCζ at time of ICSI. Fertilization, embryo development, and clinical outcomes between the two cohorts. Subsequently, we describe the clinical outcomes of couples treated solely by rhPLCζ. Participants/materials, setting, methods Thirty couples, confirmed with low level of PLCζ in the ejaculates, were offered AOA with their subsequent ICSI cycles (IRB#0712009553). Conventional AOA was performed by exposing post-ICSI oocytes to 50 µM ionomycin. The rhPLCζ-AOA method was performed by co-injecting spermatozoa with 0.4pL of a rhPLCζ (5 µg/µL) during ICSI. Chi-square tests were utilized to compare rhPLCζ-AOA versus ionomycin-AOA and rhPLCζ-AOA versus history cycles. Main results and the role of chance In the preliminary study, 9 patients were included (maternal age: 35.7 ± 6, paternal age: 36.7 ± 6). PLCζ positivity was 11.7±3.6% confirming a sperm-related oocyte activation deficiency. A total of 123 oocytes were retrieved in 9 cycles, with maturity of 78.0% (96/123). The 96 MII oocytes were allocated to be treated with ionomycin-AOA (n = 58) or rhPLCζ-AOA (n = 38). While conventional ionomycin-AOA yielded a fertilization rate at 55.2% (32/58), rhPLCζ-AOA resulted in 63.1% (24/38). Both compounds generated embryos at similar rates and one pregnancy was achieve in each cohort. On the bases of such comparable outcomes, 21 couples had 40 previous cycles that generated a fertilization rate of 18.3% (60/327), cleavage rate of 51.7% (31/60), Following the replacement of 23 embryos in 14 transfer cycles, these cycles yielded 2 clinical pregnancies, but all resulted in pregnancy loss. In the subsequent cycles with rhPLCζ-AOA (n = 32), an enhanced fertilization rate was achieved at 41.1% (116/280, P<0.00001). The treatment cycle yielded a higher cleavage rate at 80.2% (93/116, P<0.0001), and after replacing 25 embryos in 17 embryo transfer cycles, yielded 6 pregnancies and 5 of them resulted in delivered or are ongoing. Limitations, reasons for caution We demonstrated that physiological rhPLCζ-AOA achieved an excelled fertilization and clinical outcomes comparing to the traditional ionomycin method. Although further observation is needed to confirm its safety, this approach represents a more physiological method capable of achieving fertilization, higher embryo cleavage and ultimately better pregnancy outcomes. Wider implications of the findings While ICSI has gained large popularity, poor fertilization may occasionally occur. The availability of an assisted oocyte activation that utilize a native compound capable of restoring fertilization capability of the male gamete is appealing and holds great promises. Trial registration number N/A

Coupling thin layer chromatography with mass spectrometry for detection and identification of sertraline and its metabolite in the urine

The aim of the study was to detect sertraline and its metabolites in urine under standardized thin layer chromatography (TLC) screening conditions and identify the metabolites using the mass spectrometry method. Materials and methods. Urine samples, collected within 30 hours in portions of 20–50 mL, commenced from the seventh hour after the administration of a single therapeutic dose of the drug. The sample preparation process involved dilute acid hydrolysis, followed by the extraction of the native compound and metabolites with chloroform at a pH of 8–9. Thin layer chromatography studies of the extracts were conducted using four unified TLC systems recommended by The International Association of Forensic Toxicologists for general drug screening. Chromatograms were subjected to color reactions with a variety of chromogenic reagents. For the analysis of eluates from chromatograms, a Varian 1200 L mass spectrometer (Netherlands) equipped with a dual quadrupole mass analyzer was employed. Identification was performed through direct sample introduction into the ion chamber, electron-impact ionization (70 eV), and full ion scanning mode. Results. The spot of the native drug on the chromatogram was identified by the Rf, value. Metabolite of sertraline was identified as N-desmethyltrihydroxysertraline by the molecular ion peak in the mass spectrum. Conclusions. The study demonstrated the ability of TLC to detect sertraline and its metabolite, N-desmethyltrihydroxysertraline, in urine after the administration of a single therapeutic dose of the drug. The chromatographic mobility of the native compound and N-desmethyltrihydroxysertraline in the unified TLC screening systems, along with the results of their visualization using chromogenic reagents for toxicological drug screening, was determined. Furthermore, the potential of coupling TLC with mass spectrometry for the separation, detection, and confirmatory identification of sertraline and its metabolic products in urine was established.

Catechin-Functionalized Cationic Lipopolymer Based Multicomponent Nanomicelles for Lung-Targeting Delivery.

Catechins from green tea are one of the most effective natural compounds for cancer chemoprevention and have attracted extensive research. Cancer cell-selective apoptosis-inducing properties of catechins depend on efficient intracellular delivery. However, the low bioavailability limits the application of catechins. Herein, a nano-scaled micellar composite composed of catechin-functionalized cationic lipopolymer and serum albumin is constructed. Cationic liposomes tend to accumulate in the pulmonary microvasculature due to electrostatic effects and are able to deliver the micellar system intracellularly, thus improving the bioavailability of catechins. Albumin in the system acts as a biocompatible anti-plasma absorbent, forming complexes with positively charged lipopolymer under electrostatic interactions, contributing to prolonged in vivo retention. The physicochemical properties of the nano-micellar complexes are characterized, and the antitumor properties of catechin-functionalized materials are confirmed by reactive oxygen species (ROS), caspase-3, and cell apoptosis measurements. The role of each functional module, cationic polymeric liposome, and albumin is revealed by cell penetration, in vivo animal assays, etc. This multicomponent micellar nanocomposite has the potential to become an effective vehicle for the treatment of lung diseases such as pneumonia, lung tumors, sepsis-induced lung injury, etc. This study also demonstrates that it is a great strategy to create a delivery system that is both tissue-targeted and biologically active by combining cationic liposomes with the native bioactive compound catechins.

Cross-Contamination of Ignitable Liquid Residues on Wildfire Debris—Detection and Characterization in Matrices Commonly Encountered at Wildfire Scenes

Ignitable liquid residue (ILR) samples play an important role in fire investigations. Similar to other types of forensic evidence, maintaining sample integrity depends on the prevention of cross-contamination during both storage and transport. This study examines cross-contamination in ILR samples on various sample matrices (gravel, soil, wood). After inducing leaks in a controlled environment, sample analysis by GC×GC-ToF MS allowed for sensitive detection and in-depth characterization of cross-contamination processes. The potential for false positive identification of ILR is notably present due to cross-contamination. Compound transmission for a mid-range ILR (gasoline), for instance, was detectable after a 1 h exposure, with a complete profile transfer occurring after 8 h regardless of the matrix type. Visual comparisons and uptake rate calculations further confirmed matrix interaction effects taking place in the form of inherent native compound interference and adsorbate–adsorbate interaction during transmission and extraction processes for soil and wood matrices. Chemometric analysis highlighted the advantage of employing statistical analysis when investigating samples under matrix interactions by identifying several statistically significant compounds for reliably differentiating cross-contamination from background and simulated positive samples in different volatility ranges and compound classes. Untargeted analysis tentatively identified three additional compounds of interest within compound classes not currently investigated in routine analysis. The resulting classification between background, contaminated, and simulated positive samples showed no potential for false positive ILR identification and improved false negative errors, as evidenced by classification confidences progressing from 88% for targeted and 93% for untargeted to 95% for a diagnostic ratio analysis of three ratios deployed in tandem.

Computer-Aided Designing Peptide Inhibitors of Human Hematopoietic Prostaglandin D2 Synthase Combined Molecular Docking and Molecular Dynamics Simulation.

Human hematopoietic prostaglandin D2 synthase (HPGDS) is involved in the production of prostaglandin D2, which participates in various physiological processes, including inflammation, allergic reactions, and sleep regulation. Inhibitors of HPGDS have been investigated as potential anti-inflammatory agents. For the investigation of potent HPGDS inhibitors, we carried out a computational modeling study combining molecular docking and molecular dynamics simulation for selecting and virtual confirming the designed binders. We selected the structure of HPGDS (PDB ID: 2CVD) carrying its native inhibitor compound HQL as our research target. The random 5-mer peptide library was created by building the 3-D structure of random peptides using Rosetta Buildpeptide and performing conformational optimization. Molecular docking was carried out by accommodating the peptides into the location of their native binder and then conducting docking using FlexPepDock. The two peptides RMYYY and VMYMI, which display the lowest binding energy against HPGDS, were selected to perform a comparative study. The interaction of RMYYY and VMYMI against HPGDS was further confirmed using molecular dynamics simulation and aligned with its native binder, HQL. We show the selected binders to have stronger binding energy and more frequent interactions against HPGDS than HQL. In addition, we analyzed the solubility, hydrophobicity, charge, and bioactivity of the generated peptides, and we show that the selected strong binder may be further used as therapeutic drugs.

Molecular docking/dynamics simulations, MEP analysis, and pharmacokinetics prediction of some withangulatin A derivatives as allosteric glutaminase C inhibitors in breast cancer

The current study aims to understand the binding mechanism and intermolecular interactions of the novel Withangulatin A derivatives towards the allosteric site of Glutaminase C (GAC) using in silico analysis. The molecular docking and dynamics simulation results revealed that compounds L5, L8, L13, and L18 show high affinity toward the allosteric pocket of the GAC (PDB:3UO9), as confirmed by the high negative score values and hydrogen bonds. We found that these compounds interact with the most important residues and suggest a similar binding mechanism to the native compound (BPTES) and the clinical trial drug (CB-839). The combination of molecular electrostatic potential (MEP) analysis and molecular docking/dynamics studies confirms that the favorable reactive sites of these compounds establish many hydrogen bonds with active site residues of the target. Finally, pharmacokinetics prediction showed that L8 and L13 present the best ADMET profile among the selected compounds, and they share similar properties with the clinical compound CB-839. The obtained results in this investigation demonstrate that these two Withangulatin A derivatives might be used for further development as new allosteric GAC inhibitors for treating TNBC.

Fabrication and characterization of zein-sodium alginate complex nanoparticles as an effective naringenin delivery system: Physicochemical stability, solubility, antioxidant activity

Naringenin (NAR) is a native polyphenolic compound that has a variety of physiological benefits. However, the application of NAR in functional food fields is limited due to its high hydrophobicity and insufficient oral bioavailability. The objective of this study is to prepare naringenin-encapsulated zein-sodium alginate nanoparticles (NAR-Z/SA NPs) to improve the antioxidant effects of NAR by increasing the water solubility. The spherical NAR-Z/SA NPs possessed increased encapsulation efficiency (83.92 ± 0.32%) and loading capacity (18.24 ± 0.73%). The X-ray diffraction and differential scanning calorimetry results confirmed that NAR was in an amorphous state after being encapsulated. Fourier transform infrared spectroscopy revealed that hydrogen bonding, electrostatic interaction, and hydrophobic interaction drove the formation of the NAR-Z/SA NPs. Meanwhile, NAR-Z/SA NPs exhibited desirable pH (3.0–8.0), ionic (0–50 mM) and heating treatment (80°C) stability. Furthermore, NAR-Z/SA NPs had improved solubility and antioxidant activity compared with free NAR. In addition, the NAR-Z/SA NPs showed sustained release of NAR under simulated gastrointestinal conditions. These findings provide an effective choice for the broad application of NAR in food industries.

DETECTION AND IDENTIFICATION OF CITALOPRAM AND ITS BIOTRANSFORMATION PRODUCT IN THE URINE BY THIN LAYER CHROMATOGRAPHY AND MASS SPECTROM- ETRY

The conditions for detection of сitalopram and its metabolite in the urine after admin- istration of a single therapeutic dose of the antidepressant using Thin Layer Chromatography have been proposed. The Rf values of the native compound and its metabolite were determined in TLC screening systems. The сitalopram biotransformation product was identified as N- desmethylcitalopram by Mass Spectrometric study of the eluates from chromatograms. Colour reactions for сitalopram and N-desmethylcitalopram with the range of chromogenic reagents have been studied.

Investigation of Zika virus methyl transferase inhibitors using steered molecular dynamics

Zika virus (ZIKV) spread is considered a major public health threat by the World Health Organization (WHO). There are no vaccines or drugs available to control the infection of the Zika virus, therefore a highly effective medicinal molecule is urgently required. In this study, a computationally intensive investigation was performed to identify a potent natural compound that could inhibit the ZIKV NS5 methyltransferase. This research approach is based on target-based drug identification principles where the native inhibitor SAH (S-adenosylhomocysteine) of ZIKV NS5 methyltransferase was selected as a reference. High-throughput virtual screening and tanimoto similarity coefficient were applied to the natural compound library for ranking the potential candidates. The top five compounds were selected for interaction analysis, MD simulation, total binding free energy through MM/GBSA, and steered MD simulation. Among these compounds, Adenosine 5'-monophosphate monohydrate, Tubercidin, and 5-Iodotubercidin showed stable binding to the protein compared to the native compound, SAH. These three compounds also showed less fluctuations in RMSF in contrast to native compound. Additionally, the same interacting residues observed in SAH also made strong interactions with these three compounds. Adenosine 5'-monophosphate monohydrate and 5-Iodotubercidin had greater total binding free energies than the reference ligand. Moreover, the dissociation resistance of all three compounds was equivalent to that of the reference ligand. This study suggested binding properties of three-hit compounds that could be used to develop drugs against Zika virus infections. Communicated by Ramaswamy H. Sarma

Synthesis, Pharmacological Evaluation, and Molecular Modeling of Lappaconitine-1,5-Benzodiazepine Hybrids.

Diterpenoid alkaloids, originating from the amination of natural tetracyclic diterpenes, have long interested scientists due to their medicinal uses and infamous toxicity which has limited the clinical application of the native compound. Alkaloid lappaconitine extracted from various Aconitum and Delphinium species has displayed extensive bioactivities and active ongoing research to reduce its adverse effects. A convenient route to construct hybrid molecules containing diterpenoid alkaloid lappaconitine and 3H-1,5-benzodiazepine fragments was proposed. The key stage involved the formation of 5'-alkynone-lappaconitines in situ by acyl Sonogashira coupling of 5'-ethynyllappaconitine, followed by cyclocondensation with o-phenylenediamine. New hybrid compounds showed low toxicity and outstanding analgesic activity in experimental pain models, which depended on the nature of the substituent in the benzodiazepine nucleus. An analogous dependence was also shown for the antiarrhythmic activity in the epinephrine arrhythmia test in vivo. Studies on the isolated atrium have shown that the mechanism of action of the new compounds is included the blockade of beta-adrenergic receptors and potassium channels. Molecular docking analysis was conducted to determine the binding potential of target molecules with the voltage-gated sodium channel NaV1.5. All obtained results provide a basis for future rational modifications of lappaconitine, reducing side effects, while retaining its therapeutic effects.

Effects of native and particulate polyphenols on DNA damage and cell viability after UV-C exposure.

Plant polyphenols have poor water solubility, resulting in low bioavailability. In order to overcome this limitation, the drug molecules can be coated with multiple layers of polymeric materials. Microcrystals of quercetin and resveratrol coated with a (PAH/PSS)4 or (CH/DexS)4 shell were prepared using the layer-by-layer assembly method; cultured human HaCaT keratinocytes were treated with UV-C, and after that, cells were incubated with native and particulate polyphenols. DNA damage, cell viability, and integrity were evaluated by comet assay, using PrestoBlueTM reagent and lactate dehydrogenase (LDH) leakage test. The data obtained indicate that both native and particulate polyphenols added immediately after UV-C exposure increased cell viability in a dose-dependent manner; however, the efficiency of particulate quercetin was more pronounced than that of the native compound; also quercetin coated with a (CH/DexS)4 shell more effectively than the native compound reduced the number of DNA lesions in the nuclei of keratinocytes exposed to UV-C radiation; native and particulate resveratrol were ineffective against DNA damage. Quercetin reduces cell death caused by UV-C radiation and increases DNA repair capacity. Coating quercetin with (CH/DexS)4 shell markedly enhanced its impact on DNA repair.

Chinese theories of “mud” music and poetry

The article is focused on analysis of ideas of human creative activities in its connections with the spiritual life of society and state board system, which were among the fundamental problems of the Ancient Chinese thought, begging with its originative stage (mid 1st cent. BCE). The problem received a particular development in Confucian thought, and initially was applied to musical types of art (“music-Yue”), endowed with special metaphysical properties. Going from the analysis of original theoretical works the fact of formation of the holistic concept of “mud music” (yin yue) is argued. As “mud” is offered with a certain proportion of conditionality to translate the character yin, originally designated the river flow released from the coast and mixed with mud and, later, turned into a categorical term, which transmitted the totality of human Vices and related actions: immorality (including sexual behavior), debauchery, etc., and which is usually rendered in English as “excessive, licentious, obscene”. It is stated, that the spread of “mud music”, born by ethnical (barbarian) musical folklore, within the native Chinese social and cultural compound was considered by the Chinese thinkers to be the embodiment of its spiritual degradation, starting with the ruling elite. The growing popularity of “mud music” aggravated the further fall of the public moral foundations, inevitably leading to the decease of the state. At the end of this millennium, the ideas of “mud music” were transferred to poetic creativity. As a result, it is assumed that the Chinese philosophy and aesthetic thought were originally inherent in the notions of creative activity, expressing the most Vile human qualities and aspirations, and which was endowed with the ability to render debasing impact on the individual, human society and the world order.

Madecassic Acid Ameliorates the Progression of Osteoarthritis: An in vitro and in vivo Study.

Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment besides late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Madecassic acid (MA) is the first native triterpenoid compound extracted from Centella asiatica, which has a variety of anti-inflammatory effects. However, the role of MA in OA therapy has not been reported. This study aimed to explore whether MA could suppress the inflammatory response, preserve and restore chondrocyte functions, and ameliorate the progression of OA in vitro and in vivo. Rat primary chondrocytes were treated with IL-1β to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of MA at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 10 µM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and Western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with MA into the knee articular cavity. We found that MA could down-regulate the IL-1β-induced up-regulation of COX-2, iNOS and IL-6 and restore the cytoskeletal integrity of chondrocytes treated with IL-1β. Moreover, MA protects chondrocytes from IL-1β-induced ECM degradation by upregulating ECM synthesis related protein expression, including collagen-II and ACAN, and further down-regulating ECM catabolic related protein expression, including MMP-3 and MMP-13. Furthermore, we found that NF-κB/IκBα and PI3K/AKT signaling pathways were involved in the regulatory effects of MA on the inflammation inhibition and promotion of ECM anabolism on IL-1β-induced chondrocytes. These findings suggest that MA appears to be a potentially small molecular drug for rat OA.

Activity of singly and doubly modified derivatives of C20-epi-salinomycin against Staphylococcus strains

Natural polyether ionophore salinomycin (Sal) has been widely used in veterinary medicine as an antibiotic effective in the treatment of coccidian protozoa and Gram-positive bacteria. Moreover, chemical modification of the Sal structure has been found to be a promising strategy to generate semisynthetic analogs with biological activity profiles improved relative to those of the native compound. In this context, we synthesized and thoroughly evaluated the antibacterial potential of a library of C1/C20 singly and doubly modified derivatives of C20-epi-salinomycin, that is, analogs of Sal with inversed stereochemistry at the C20 position. Among the synthesized analog structures, the most promising antibacterial active agents were those obtained via regioselective O-acylation of C20-epi-hydroxyl, particularly esters 7, 9, and 11. Such C20 singly modified compounds showed excellent inhibitory activity against planktonic staphylococci, both standard and clinical strains, and revealed potential in preventing the formation of bacterial biofilms. In combination with their non-genotoxic properties, these Sal derivatives represent attractive candidates for further antimicrobial drug development.

Effects of citronellal on growth and enterotoxins production in Staphylococcus aureus ATCC 29213

Staphylococcus aureus (S. aureus) is known to be one of the most common foodborne pathogens capable of secreting a wide range of exotoxins such as enterotoxin, which severely threatens the health of consumers. Over the past few years, the development of safe and effective strategies in inhibiting the growth and enterotoxins generation of S. aureus in food turns out to be the research focus and emphasis. This research explores citronellal (CIT), a native compound with extensive existence in spices, which could effectively inhibit the growth and enterotoxins generation of S. aureus (ATCC 29213). Results from minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill curves, showed that CIT could tremendously inhibit the growth of S. aureus. Analysis on hemolysin showed that CIT at sub-MIC could significantly (p < 0.05) inhibit the hemolytic activity of S. aureus. As revealed by the results of ELISA, the production of enterotoxins in the culture supernatant and pork meat decreased significantly (p < 0.05) after exposure to CIT at sub-MIC. Furthermore, a significant (p < 0.05) decrease in dose-dependent was found in the transcription levels of virulence-related genes. In all, CIT proved to be a possible inhibitor of the growth and enterotoxins production of S. aureus with highly promising application in the food industry.

Reframing schizophrenia: Altering our perceptions?

Staphylococcus aureus (S. aureus) is known to be one of the most common foodborne pathogens capable of secreting a wide range of exotoxins such as enterotoxin, which severely threatens the health of consumers. Over the past few years, the development of safe and effective strategies in inhibiting the growth and enterotoxins generation of S. aureus in food turns out to be the research focus and emphasis. This research explores citronellal (CIT), a native compound with extensive existence in spices, which could effectively inhibit the growth and enterotoxins generation of S. aureus (ATCC 29213). Results from minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill curves, showed that CIT could tremendously inhibit the growth of S. aureus. Analysis on hemolysin showed that CIT at sub-MIC could significantly (p < 0.05) inhibit the hemolytic activity of S. aureus. As revealed by the results of ELISA, the production of enterotoxins in the culture supernatant and pork meat decreased significantly (p < 0.05) after exposure to CIT at sub-MIC. Furthermore, a significant (p < 0.05) decrease in dose-dependent was found in the transcription levels of virulence-related genes. In all, CIT proved to be a possible inhibitor of the growth and enterotoxins production of S. aureus with highly promising application in the food industry.