Μg mL-1 Research Articles

Isolation of anthraquinone derivatives from Rubia cordifolia (Rubiaceae) and their bioactivities against plant pathogenic microorganisms.

The discovery of antimicrobial ingredients from natural products could be an effective way to create novel fungicides. Rubia cordifolia L., a traditional Chinese herb, may have antimicrobial effects on plant pathogens according to our previous screening study. Rubia cordifolia L. extracts had moderate inhibitory effects on apple Valsa canker (Valsa mali) and tomato grey mould (Botrytis cinerea) at a concentration of 10 mg mL-1. With the use of bioguided isolation methods, eight compounds (1-8) were obtained, including the new compound 2,2,6-trimethyl-6-(4-methylphenyl)-tetrahydropyrano- 3-ol (7), and seven quinone derivatives. Two compounds, mollugin (1) and 1,3,6-trihydroxy-2-methylanthraquinone (6), were found to exhibit outstanding antifungal activities against V. mali and Phytophthora capsici Leon. The half maximal effective concentration (EC50) of compound 1 and compound 6 against V. mali were 79.08 and 81.78 μg mL-1, respectively, and the EC50 of compound 6 against P. capsici was 4.86 μg mL-1. Compound 1 also showed excellent activity against tobacco mosaic virus (TMV). The inactive, inductive, protective and curative activities against TMV were 84.29%, 83.38%, 86.81%, and 60.02%, respectively, at a concentration of 500 μg mL-1, which were all close to or greater than that of the positive control (100 μg mL-1 chitosan oligosaccharide, COS). Mollugin and 1,3,6-trihydroxy-2-methylanthraquinone are potentially valuable active compounds that lay a foundation for research on botanical fungicide products derived from R. cordifolia L. and provide lead structures for quinone derivative synthesis and structural modification. © 2024 Society of Chemical Industry.

Dual modulation of blue-fluorescent carbon dots for simultaneous detection of topotecan and pantoprazole.

This study introduces a novel approach for the simultaneous determination of topotecan (TOP) and pantoprazole (PNT), two drugs whose interaction is critical in clinical applications. The significance of this study originates from the need to understand the pharmacokinetic changes of TOP after PNT administration, which can inform necessary dose adjustments of TOP. To achieve this, nitrogen blue emissive carbon dots (B@NCDs) were produced and employed due to their unique fluorescent properties. When TOP is added to B@NCDs, it exhibits strong native fluorescence at 545 nm without influencing the B@NCDs' fluorescence at 447 nm. Conversely, PNT causes quenching of B@NCDs fluorescence, a property that enables the distinct detection of both drugs. The B@NCDs were fully characterized using different techniques, including ultraviolet-visible spectrophotometry, fluorescence analysis, X-ray diffraction (XRD), transmission electron microscopy (TEM), and FTIR spectroscopy. The proposed method demonstrated excellent linearity, selectivity, and sensitivity, with low detection limits (LOD, S/N = 3); 0.0016 μg mL-1 for TOP and 0.36 μg mL-1 for PNT. Applied to spiked rabbit plasma samples, this method offers a new approach for evaluating the pharmacokinetic interaction between TOP and PNT. It enables the determination of all pharmacokinetic parameters of TOP before and after coadministration with PNT, providing essential insights into whether dose adjustments are necessary. This research not only contributes to the field of drug monitoring and interaction studies but also exemplifies the potential of B@NCDs in complex biological matrices, paving the way for further pharmacological and therapeutic applications.

Innovation of 6-sulfonamide-2H-chromene derivatives as antidiabetic agents targeting α-amylase, α-glycosidase, and PPAR-γ inhibitors with in silico molecular docking simulation.

A new series of 2-imino or 2-oxo-2H-chromene-6-sulfonamide derivatives 2-9 with potential anti-diabetic activity were designed and synthesized. The new 6-sulfonamide chromenes were synthesized by reacting 3-formyl-4-hydroxybenzenesulfonyl chloride with activated methylene derivatives in the presence of ammonium acetate as a catalyst. The structure of the products was confirmed by spectroscopic analysis. All the designed derivatives 2-9 were evaluated for their activity against α-amylase and exhibited inhibitory percentage values higher than 93% at 100 μg mL-1. Additionally, the IC50 values represented a variable degree of activity with two derivatives 2 and 9 exhibiting the most promising derivative results with IC50 values of 1.76 ± 0.01 and 1.08 ± 0.02 μM, respectively, compared to Acarbose (IC50 = 0.43 ± 0.01 μM). Additionally, these derivatives showed potency against the α-glucosidase enzyme with IC50 values of 0.548 ± 0.02 and 2.44 ± 0.09 μg mL-1, compared to Acarbose (0.604 ± 0.02 μg mL-1). Moreover, the in vitro PPAR-γ transactivation assay revealed that chromene-6-sulfonamide derivatives 2 and 9 exhibited potential PPAR-γ activity with IC50 values of 3.152 ± 0.03 and 3.706 ± 0.32 μg mL-1, respectively, compared to Pioglitazone (4.884 ± 0.29 μg mL-1). This indicates that these derivatives have insulin sensitivity and glucose metabolism activity. The in silico ADMET prediction showed that these derivatives have an acceptable range of oral bioavailability, drug-likeness, and a safe toxicity profile, including being non-cytotoxic, non-mutagenic, non-immunotoxic, and non-carcinogenic. Finally, computational docking analysis demonstrated the ability of these derivatives to interact with α-amylase, α-glucosidase, and PPAR-γ enzymes, with confirmed successful placement due to good binding energy values and various interactions within the pocket.

Design, synthesis and Anti-PVY activity of planar chiral thiourea derivatives incorporated with [2.2]Paracyclophane.

Potato virus Y (PVY) is a prominent representative of plant viruses. It can inflict severe damage upon Solanaceae plants, leading to global dissemination and substantial economic losses. To discover new antiviral agents, a class of planar chiral thiourea molecules through the key step of N-heterocyclic carbene-catalyzed nitrile formation reaction was synthesized with excellent optical purities for antiviral evaluations against plant virus PVY. The absolute configurations of the planar chiral compounds exhibited obvious distinctions in the anti-PVY activities. Notability, compound (S)-4u exhibited remarkable curative activities against PVY, with a half maximal effective concentration (EC50) of 349.3 μg mL-1, which was lower than that of the ningnanmycin (NNM) (EC50 = 400.8 μg mL-1). Additionally, The EC50 value for the protective effects of (S)-4u was 146.2 μg mL-1, which was superior to that of NNM (276.4 μg mL-1). Furthermore, the mechanism-of-action of enantiomers of planar chiral compound 4u was investigated through molecular docking, defensive enzyme activity tests and chlorophyll content tests. Biological mechanism studies have demonstrated that the configuration of planar chiral target compounds plays a crucial role in the molecular interaction with PVY-CP, enhancing the activity of defense enzymes and affecting chlorophyll content. The current study has provided significant insights into the roles played by planar chiralities in plant protection against viruses. This paves the way for the development of novel green pesticides bearing planar chiralities with excellent optical purities. © 2024 Society of Chemical Industry.

In vitro activity of plazomicin and other aminoglycosides against Klebsiella pneumoniae multidrug-resistant strains.

Plazomicin is a new aminoglycoside with broad-spectrum activity against multidrug-resistant strains. The aim of this study was to assess the susceptibility of the K. pneumoniae strains to plazomicin and other aminoglycosides. The activity of plazomicin in combination with ceftazidim-avibactam or meropenem with selected strains was evaluated. The study involved 60 ESβL-positive K. pneumoniae isolates and 50 carbapenemase-positive. The susceptibility to aminoglycosides was tested using the gradient strip. The in vitro activities of plazomicin and ceftazidim-avibactam or meropenem were evaluated using the MTSTM cross synergy method. Plazomicin exhibited high activity against K. pneumoniae with MICs ranging from 0.19 to 4 µg ml-1 for ESβL-positive strains and from 0.25 to 256 µg ml-1 for carbapenemase-positive strains. No antagonism was identified with any combinations. Plazomicin demonstrated excellent in vitro activity against analyzed strains, suggesting that this antibiotic may be an effective therapeutic option in the treatment of infections caused by MDR K. pneumoniae strains.

New liposidomycin congeners produced by Streptomyces sp. TMPU-20A065, anti-Mycobacterium avium complex agents with therapeutic efficacy in a silkworm infection model.

Three new liposidomycin congeners (1, 2, and 4), together with 14 known liposidomycins (3 and 5-17), were isolated from the culture broth of Streptomyces sp. TMPU-20A065 as anti-Mycobacterium avium complex agents. The structures of liposidomycins were elucidated by spectroscopic analyses, including NMR and MS. Compounds 1, 2, and 4 belong to type-I liposidomycin-containing sulfate groups and methylglutaric acid, each with a different acyl side chain in the structure. Compounds 1-17 exhibited in vitro anti-M. avium and M. intracellulare activities with MIC values ranging between 2.0 and 64 μg ml-1. Furthermore, 1-17 exerted potent therapeutic effects in an in vivo-mimic silkworm infection model with ED50 values ranging between 0.12 and 3.7 μg larva-1 g-1.

Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV-1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion-stabilized HIV-1 envelope (Env) trimer, BG505 DS-SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4-binding site (CD4bs) of vulnerability. Two of the vaccine-elicited CD4bs-targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a-hinge region and human IgG1-constant region (G36×3-IgG2a and R27×3-IgG2a), neutralized 96% of a multiclade 208-strain panel at geometric mean IC80s of 0.314 and 0.033µg mL-1, respectively. Cryo-EM structures of these nanobodies in complex with Env trimer revealed the two nanobodies to neutralize HIV-1 by mimicking the recognition of the CD4 receptor. To enhance their neutralizing potency and breadth, nanobodies are linked to the light chain of the V2-apex-targeting broadly neutralizing antibody, CAP256V2LS. The resultant human-llama bispecific antibody CAP256L-R27×3LS exhibited ultrapotent neutralization and breadth exceeding other published HIV-1 broadly neutralizing antibodies, with pharmacokinetics determined in FcRn-Fc mice similar to the parent CAP256V2LS. Vaccine-elicited llama nanobodies, when combined with V2-apex broadly neutralizing antibodies, may therefore be able to fulfill anti-HIV-1 therapeutic and prophylactic clinical goals.

Characterization of arsenic species by liquid sampling-atmospheric pressure glow discharge ionization mass spectrometry.

A liquid sampling-atmospheric pressure glow discharge (LS-APGD) ionization source operating at a nominal power of 30 W and solution flow rate of 30 µL min-1 and supported in a He sheath gas flow rate of 500 mL min-1 was interfaced to an Orbitrap mass spectrometer and assessed for use in rapid identification of inorganic and organic arsenic species, including As(III), As(V), monomethylarsonic acid, dimethylarsinic acid, and arsenobetaine in a 2% (v/v) nitric acid medium. Mass spectral acquisition in low-resolution mode, using only the ion trap analyzer, provided detection of protonated molecular ions for AsBet (m/z 179), DMA (m/z 139), MMA (m/z 141), and As(V) (m/z 143). As(III) is oxidized to As(V), likely due to in-source processes. Typical fragmentation of these compounds resulted in the loss of either water or methyl groups, as appropriate, i.e., introducing DMA also generated ions corresponding to MMA and As(V) as dissociation products. Structure assignments were also confirmed by high-resolution Orbitrap measurements. Spectral fingerprint assignments were based on the introduction of solutions containing 5 µg mL-1 of each arsenic compound.

Combined effect of SAR-endolysin LysKpV475 with polymyxin B and Salmonella bacteriophage phSE-5.

Endolysins are bacteriophage (or phage)-encoded enzymes that catalyse the peptidoglycan breakdown in the bacterial cell wall. The exogenous action of recombinant phage endolysins against Gram-positive organisms has been extensively studied. However, the outer membrane acts as a physical barrier when considering the use of recombinant endolysins to combat Gram-negative bacteria. This study aimed to evaluate the antimicrobial activity of the SAR-endolysin LysKpV475 against Gram-negative bacteria as single or combined therapies, using an outer membrane permeabilizer (polymyxin B) and a phage, free or immobilized in a pullulan matrix. In the first step, the endolysin LysKpV475 in solution, alone and combined with polymyxin B, was tested in vitro and in vivo against ten Gram-negative bacteria, including highly virulent strains and multidrug-resistant isolates. In the second step, the lyophilized LysKpV475 endolysin was combined with the phage phSE-5 and investigated, free or immobilized in a pullulan matrix, against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The bacteriostatic action of purified LysKpV475 varied between 8.125 μg ml-1 against Pseudomonas aeruginosa ATCC 27853, 16.25 μg ml-1 against S. enterica Typhimurium ATCC 13311, and 32.50 μg ml-1 against Klebsiella pneumoniae ATCC BAA-2146 and Enterobacter cloacae P2224. LysKpV475 showed bactericidal activity only for P. aeruginosa ATCC 27853 (32.50 μg ml-1) and P. aeruginosa P2307 (65.00 μg ml-1) at the tested concentrations. The effect of the LysKpV475 combined with polymyxin B increased against K. pneumoniae ATCC BAA-2146 [fractional inhibitory concentration index (FICI) 0.34; a value lower than 1.0 indicates an additive/combined effect] and S. enterica Typhimurium ATCC 13311 (FICI 0.93). A synergistic effect against S. enterica Typhimurium was also observed when the lyophilized LysKpV475 at ⅔ MIC was combined with the phage phSE-5 (m.o.i. of 100). The lyophilized LysKpV475 immobilized in a pullulan matrix maintained a significant Salmonella reduction of 2 logs after 6 h of treatment. These results demonstrate the potential of SAR-endolysins, alone or in combination with other treatments, in the free form or immobilized in solid matrices, which paves the way for their application in different areas, such as in biocontrol at the food processing stage, biosanitation of food contact surfaces and biopreservation of processed food in active food packing.

Synthesis, antifungal evaluation, 2D-Quantitative structure activity relationship and molecular docking studies of isoxazole derivatives as potential fungicides.

Sheath blight and bakanae disease, prominent among emerging rice ailments, exert a profound impact on rice productivity, causing severe impediments to crop yield. Excessive use of older fungicides may lead to the development of resistance in the pathogen. Indeed, a pressing and immediate need exists for novel, low-toxicity and highly selective fungicides that can effectively combat resistant fungal strains RESULTS: A series of 20 isoxazole derivatives were synthesized using alkoxy/halo acetophenones and N,N-dimethylformamidedimethylacetal. These compounds were characterized by various spectroscopic techniques viz. 1H NMR, 13C NMR and LC-HRMS and were evaluated for their fungicidal activity against Rhizoctonia solani and Fusarium fujikuroi. Compound 5n (5-(2-chlorophenyl) isoxazole) exhibited highest activity (ED50 = 4.43 μg mL-1) against R. solani, while 5p (5-(2,4-dichloro-2-hydroxylphenyl) isoxazole) exhibited highest activity (ED50 = 6.7 μg mL-1) against F. fujikuroi. 2D-Quantitative Structural Activity Relationship (2D-QSAR) analysis, particularly MLR (Model 1), highlighted chi6chain and DistTopo as the key descriptors influencing fungicidal activity. Molecular docking studies revealed the potential of these isoxazole derivatives as novel fungicides targeting sterol 14α-demethylase enzyme, suggesting their importance as crucial intermediates for the development of novel and effective fungicides. All test compounds were effective in inhibiting both fungi, according to the QSAR model, various descriptors such as structural, molecular shape analysis, electronic, and thermodynamic play an important role. Molecular docking studies confirmed that these compounds can potentially replace commercially available fungicides and help control fungal pathogens in rice crops effectively. This article is protected by copyright. All rights reserved.

Optimization of Cyanocobalamin (Vitamin B12) Sorption onto Mesoporous Superparamagnetic Iron Oxide Nanoparticles.

The techniques used to detect and quantify cyanocobalamin (vitamin B12) vary considerably in terms of detection sensitivity, from the most sensitive, based on radioisotopes and mass spectrometry (MS) with limits of detection (LOD) in fg mL-1, to fluorescence (FL) and surface plasmon resonance (SPR) biosensors with LOD values in the range of a few µg mL-1. For accurate quantification of an analyte present at trace levels in complex biological matrices, a selective separation and enrichment step is required to overcome matrix interferences and ensure sufficient detection sensitivity. In this study, iron oxide magnetic nanoparticles (IONPs) were used for the extraction and initial preconcentration of cyanocobalamin (vitamin B12). In the dependence of the magnetization on the H-field (hysteresis loop), no coercivity and remanence values were found at 300 K, indicating the superparamagnetic properties of the tested IONPs. Perfluorinated acids were used as amphiphilic agents to allow the sorption of cyanocobalamin onto the IONPs. FT-IR/ATR spectroscopy was used to confirm the sorption of cyanocobalamin on the IONPs. The influence of the addition of a homologous series of perfluorinated acids such as trifluoroacetic acid (TFAA), heptafluorobutyric acid (HFBA), and trichloroacetic acid (TCAA) to the extraction mixture was tested considering their type, mass, and time required for effective sorption. The adsorption kinetics and isotherm, described by the Freundlich and Langmuir equations, were analyzed. The maximum adsorption capacity (qm) exceeded 6 mg g-1 and was 8.9 mg g-1 and 7.7 mg g-1 for HFBA and TCAA, respectively, as the most efficient additives. After the desorption process using aqueous KH2PO4 solution, the sample was finally analyzed spectrophotometrically and chromatographically. The IONP-based method was successfully applied for the isolation of cyanocobalamin from human urine samples. The results showed that the developed approach is simple, cheap, accurate, and efficient for the determination of traces of cyanocobalamin in biological matrices.

The stunting effect of an oxylipins-containing macroalgae extract on sea urchin reproduction and neuroblastoma cells viability

Different bioactive molecules extracted from macroalgae, including oxylipins, showed interesting potentials in different applications, from healthcare to biomaterial manufacturing and environmental remediation. Thus far, no studies reported the effects of oxylipins-containing macroalgae extracts on embryo development of marine invertebrates and on neuroblastoma cancer cells. Here, the effects of an oxylipins-containing extract from Ericaria brachycarpa, a canopy-forming brown algae, were investigated on the development of Arbacia lixula sea urchin embryos and on SH-SY5Y neuroblastoma cells viability. Embryos and cells were exposed to concentrations covering a full 0-100% dose-response curve, with doses ranging from 0 to 40 μg mL-1 for embryos and from 0 to 200 μg mL-1 for cells. These natural marine toxins caused a dose-dependent decrease of normal embryos development and of neuroblastoma cells viability. Toxicity was higher for exposures starting from the gastrula embryonal stage if compared to the zygote and pluteus stages, with an EC50 significantly lower by 33 and 68%, respectively. Embryos exposed to low doses showed a general delay in development with a decrease in the ability to calcify, while higher doses caused 100% block of embryo growth. Exposure of SH-SY5Y neuroblastoma cells to 40 μg mL-1 for 72 h caused 78% mortality, while no effect was observed on their neuronal-like cells derivatives, suggesting a selective targeting of proliferating cells. Western Blot experiments on both model systems displayed the modulation of different molecular markers (HSP60, HSP90, LC3, p62, CHOP and cleaved caspase-7), showing altered stress response and enhanced autophagy and apoptosis, confirmed by increased fragmented DNA in apoptotic nuclei. Our study gives new insights into the molecular strategies that marine invertebrates use when responding to their environmental natural toxins and suggests the E. brachycarpa’s extract as a potential source for the development of innovative, environmentally friendly products with larvicide and antineoplastic activity.

Au-Based Nanoparticles Enhance Low Temperature Tolerance in Wheat by Regulating Some Physiological Parameters and Gene Expression.

One of the key problems of biology is how plants adapt to unfavorable conditions, such as low temperatures. A special focus is placed on finding ways to increase tolerance in important agricultural crops like wheat. Au-based nanoparticles (Au-NPs) have been employed extensively in this area in recent years. Au-NPs can be produced fast and easily using low-cost chemical reagents. When employed in microdoses, Au-NPs are often non-toxic to plants, animals, and people. In addition, Au-NPs mainly have favorable impacts on plants. In this study, we investigated the effect of Au-NP seed nanopriming (diameter 15.3 nm, Au concentration 5-50 µg mL-1) on cold tolerance, as well as some physiological, biochemical and molecular parameters, of cold-sustainable wheat (Triticum aestivum L.) genotype Zlata. The treatment with Au-NPs improved tolerance to low temperatures in control conditions and after cold hardening. Au-NPs treatment boosted the intensity of growth processes, the quantity of photosynthetic pigments, sucrose in leaves, and the expressions of encoded RuBisCo and Wcor15 genes. The potential mechanisms of Au-NPs' influence on the cold tolerance of wheat varieties were considered.

Amine Switchable Hydrophilic Solvent Vortex-Assisted Homogeneous Liquid-Liquid Microextraction and GC-MS for the Enrichment and Determination of 2, 6-DIPA Additive in Biodegradable Film.

2, 6-diisopropylaniline (2, 6-DIPA) is a crucial non-intentionally organic additive that allows the assessment of the production processes, formulation qualities, and performance variations in biodegradable mulching film. Moreover, its release into the environment may have certain effects on human health. Hence, this study developed simultaneous heating hydrolysis-extraction and amine switchable hydrophilic solvent vortex-assisted homogeneous liquid-liquid microextraction for the gas chromatography-mass spectrometry analysis of the 2, 6-DIPA additive and its corresponding isocyanates in poly(butylene adipate-co-terephthalate) (PBAT) biodegradable agricultural mulching films. The heating hydrolysis-extraction conditions and factors influencing the efficiency of homogeneous liquid-liquid microextraction, such as the type and volume of amine, homogeneous-phase and phase separation transition pH, and extraction time were investigated and optimized. The optimum heating hydrolysis-extraction conditions were found to be a H2SO4 concentration of 2.5 M, heating temperature of 87.8 °C, and hydrolysis-extraction time of 3.0 h. As a switchable hydrophilic solvent, dipropylamine does not require a dispersant. Vortex assistance is helpful to speed up the extraction. Under the optimum experimental conditions, this method exhibits a better linearity (0.0144~7.200 μg mL-1 with R = 0.9986), low limit of detection and quantification (0.0033 μg g-1 and 0.0103 μg g-1), high extraction recovery (92.5~105.4%), desirable intra- and inter-day precision (relative standard deviation less than 4.1% and 4.7%), and high enrichment factor (90.9). Finally, this method was successfully applied to detect the content of the additive 2, 6-DIPA in PBAT biodegradable agricultural mulching films, thus facilitating production process monitoring or safety assessments.

METHOD DEVELOPMENT AND VALIDATION FOR QUANTIFICATION OF IMATINIB MESYLATE SPIKED IN VITRO SALIVA BY LC-MS/MS

A novel, sensible, rapid, reliable and economical analytical hyphenated LC-MS/MS method has been developed as a key for the safety surveillance in chronic leukemia patients, and as a part of therapeutic drug monitoring of imatinib mesylate in human saliva. Imatinib mesylate or imatinib methane sulfonate is a tyrosine kinase inhibitor, apoptosis inducer and also known to be an anticoronaviral agent. Imatinib mesylate is a monomesylate salt of imatinib used for the treatment of gastrointestinal tumors and chronic myelogenous leukemia, and also in other complex malignancies. The lmax of imatinib mesylate was observed at 258 nm by UV spectrometry, establishing a very good linearity along with sensitivity. The detection limit (LOD) =0.2925 µg mL-1 and quantitation limit (LOQ)= 0.8977 µg mL- ¹ were obtained from the linear concentrations taken in the range of 2-12 µg mL-1. The correlation coefficient (r2 ) found was 0.999. The method validation parameters according to ICH Q2 (R1) were performed. The developed method described here, UPLC-MS/MS, was found to be novel, sensitive and rapid with improved results when successfully tested for human saliva samples without significant differences in the steady state imatinib mesylate concentrations. Current method could overcome the safety issues during therapeutic drug monitoring and pharmacokinetic behavior of the drug when tested clinically.

Rational Design of Coordination Polymers Composited Hollow Multishelled Structures for Drug Delivery.

Multifunctional drug delivery systems (DDS) are in high demand for effectively targeting specific cells, necessitating excellent biocompatibility, precise release mechanisms, and sustained release capabilities. The hollow multishelled structure (HoMS) presents a promising solution, integrating structural and compositional design for efficient DDS development amidst complex cellular environments. Herein, starting from a Fe-based metal-organic framework (MOF), amorphous coordination polymers (CP) composited HoMS with controlled shell numbers are fabricated by balancing the rate of MOF decomposition and shell formation. Fe-CP HoMS loaded with DOX is utilized for synergistic chemotherapy and chemodynamic therapy, offering excellent responsive drug release capability (excellent pH-triggered drug release 82% within 72h at pH 5.0 solution with doxorubicin (DOX) loading capacity of 284mg g-1). In addition to its potent chemotherapy attributes, Fe-CP-HoMS possesses chemodynamic therapy potential by continuously catalyzing H2O2 to generate ·OH species within cancer cells, thus effectively inhibiting cancer cell proliferation. DOX@3S-Fe-CP-HoMS, at a concentration of 12.5µg mL-1, demonstrates significant inhibitory effects on cancer cells while maintaining minimal cytotoxicity toward normal cells. It is envisioned that CP-HoMS could serve as an effective and biocompatible platform for the advancement of intelligent drug delivery systems in the realm of cancer therapy.

Development of a Simultaneous Normal-Phase HPLC Analysis of Lignans, Tocopherols, Phytosterols, and Squalene in Sesame Oil Samples.

The objective of this study was to develop a simultaneous analytical method for the determination of lignans, tocols, phytosterols, and squalene using high-performance liquid chromatography coupled with a diode array and fluorescence detector (HPLC-DAD-FLD). The method employed a VertisepTM UPS silica HPLC column (4.6 × 250 mm, 5 µm) with a mobile phase mixture of n-hexane/tetrahydrofuran/2-propanol. This approach enabled the simultaneous analysis of ten compounds within 22 min. The linear correlation (R2) exceeded 0.9901. The limit of detection (LOD) and limit of quantitation (LOQ) were up to 0.43 µg mL-1 for lignans and tocopherols and up to 326.23 µg mL-1 for phytosterol and squalene. The precision and accuracy of the intra-day and inter-day variation were less than 1.09 and 3.32% relative standard deviations (RSDs). Furthermore, the developed method was applied for the analysis of targeted compounds in twenty-eight sesame oil samples (1775-8965 µg g-1 total lignans, 29.7-687.9 µg g-1 total tocopherols, 2640-9500 µg g-1 phytosterol, and 245-4030 µg g-1 squalene). The HPLC method that has been developed was proven to be a reliable and effective tool for the determination of those functional compounds among sesame oil samples.

Rhein kills Actinobacillus pleuropneumoniae, reduces biofilm formation, and effectively treats bacterial lung infections in mice.

Background. Actinobacillus pleuropneumoniae, a member of the Pasteurellaceae family, is known for its highly infectious nature and is the primary causative agent of infectious pleuropneumonia in pigs. This disease poses a considerable threat to the global pig industry and leads to substantial economic losses due to reduced productivity, increased mortality rates, and the need for extensive veterinary care and treatment. Due to the emergence of multi-drug-resistant strains, Chinese herbal medicine is considered one of the best alternatives to antibiotics due to its unique mechanism of action and other properties. As a type of Chinese herbal medicine, Rhein has the advantages of a wide antibacterial spectrum and is less likely to develop drug resistance, which can perfectly solve the limitations of current antibacterial treatments.Methods. The killing effect of Rhein on A. pleuropneumoniae was detected by fluorescence quantification of differential expression changes of key genes, and scanning electron microscopy was used to observe the changes in A. pleuropneumoniae status after Rhein treatment. Establishing a mouse model to observe the treatment of Rhein after A. pleuropneumoniae infection.Results. Here, in this study, we found that Rhein had a good killing effect on A. pleuropneumoniae and that the MIC was 25 µg ml-1. After 3 h of action, Rhein (4×MIC) completely kills A. pleuropneumoniae and Rhein has good stability. In addition, the treatment with Rhein (1×MIC) significantly reduced the formation of bacterial biofilms. Therapeutic evaluation in a murine model showed that Rhein protects mice from A. pleuropneumoniae and relieves lung inflammation. Quantitative RT-PCR (Quantitative reverse transcription polymerase chain reaction is a molecular biology technique that combines both reverse transcription and polymerase chain reaction methods to quantitatively detect the amount of a specific RNA molecule) results showed that Rhein treatment significantly downregulated the expression of the IL-18 (Interleukin refers to a class of cytokines produced by white blood cells), TNF-α, p65 and p38 genes. Along with the downregulation of genes such as IL-18, it means that Rhein has an inhibitory effect on the expression of these genes, thereby reducing the activation of inflammatory cells and the production of inflammatory mediators. This helps reduce inflammation and protects tissue from further damage.Conclusions. This study reports the activity of Rhein against A. pleuropneumoniae and its mechanism, and reveals the ability of Rhein to treat A. pleuropneumoniae infection in mice, laying the foundation for the development of new drugs for bacterial infections.

A comprehensive study on Geranium robertianum L. antibacterial potential.

The research aimed to optimize the ultrasound-assisted extraction of secondary metabolites and the antibacterial activity of the plant species Geranium robertianum. The phytochemical profiles of the optimized extracts, as well as their antibacterial and synergistic activity with an antibiotic and their potential mechanisms of action and cytotoxicity, were examined. Response Surface Methodology was used to optimize extraction conditions. Optimized ethanol and acetone extracts were tested via microdilution, checkerboard, time-kill kinetics, and cell membrane permeability methods. The extracts displayed broad antibacterial activity with minimum inhibitory concentrations ranging from 1.25 to 20mg ml-1. In addition, the extract synergistically reacted with gentamicin against gentamicin-resistant strains of Escherichia coli and Staphylococcus aureus, enhancing the efficacy of the antibiotic up to 32-fold. The extracts demonstrated strain-dependent bactericidal activity in a 24-h time interval. They increase the permeability of the cell membrane, thus disrupting its normal functioning. The cytotoxic concentration (CC50) on human keratinocytes was 1771.24±5.78µg ml-1 for ethanol extract, and 958.01±6.14µg ml-1 for acetone extract. Kaempferol, ellagic acid, quercetin, and rutin were recognized as the main components in both extracts. The findings of this study indicate that the extracts of G. robertianum can be considered as potential natural antibacterial agents in the control of microorganisms.

The extract of Cavendish banana (Musa acuminata) peel as antioxidant and anti-aging agents in model yeast Schizosaccharomyces pombe

Banana peel is one of the wastes that can be explored for various applications. Cavendish is among the most highly consumed bananas in the world, which implies a high amount of banana peel waste. Our study evaluated the potential of Cavendish banana peels as the source of antioxidant and anti-aging agents. Antioxidant was extracted using three different solvents, i.e., water, ethyl acetate, and methanol. Each extract was then assayed for antioxidant activity in vitro using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The antioxidant and anti-aging activity of the extracts were further evaluated at the cellular level using the yeast Schizosaccharomyces pombe as a model. Our data indicated that the methanol extract of banana peel showed the highest antioxidant activity with an IC50 value of 253.8 µg mL-1 compared to ethyl acetate and water, yet it was considered weak. Interestingly, the methanol extract (600 ppm) showed antioxidant and anti-aging activities at cellular levels in yeast S. pombe. Therefore, this research reveals the potential for developing banana peel methanol extract as a component of pharmaceutical or cosmetic products with antioxidant and anti-aging properties.