Search Results (2,040)

Lathyrus odoratus L., commonly known as sweet pea, is a plant with a distinctive aroma that can develop in various habitats. An analysis of the aromatic profile of the species was conducted using the HS-SPME (solid-phase microextraction headspace) technique. This study aimed to explore the composition of and variation in the floral scent emissions of L. odorathus. The floral scents from fresh flowers were collected over different months and analyzed using gas chromatography coupled with mass spectrometry on apolar and polar stationary phase columns. In the apolar column, the majority compounds included linalool (19.27–5.79%), α-trans-bergamotene (29.4–14.21%), and phenyl ethyl alcohol (30.01–1.56%), while on the polar column, the predominant compounds included myrcene (13.25%), (E,E)-α-farnesene (26.33–8.16%), α-trans-bergamotene (42.09–24.82%), and others. This investigation was complemented by enantioselective analysis using a chiral phase based in cyclodextrins, which revealed the presence of (1R)-(+)-α-pinene, (S)-(−)-limonene, (R)-(+)-germacrene D, and (R)-(E)-nerolidol as enantiomerically pure components and linalool as a racemic mixture. Notably, the principal component analysis (PCA) and heatmap revealed variations among the chemical compounds collected at different harvest times. This demonstrates that temporal factors indeed impact chemical compound production. Furthermore, research on the aromatic properties of flowers provides a theoretical basis for studying and improving the components of their scent. Full article

Background/Objectives: Nitazoxanide (NTX) exhibits promising therapeutic potential; its effectiveness is constrained by its low oral bioavailability due to its poor water solubility and limited permeability. Methods: This study focused on developing a complex of NTX with β-cyclodextrins (β-CDs), specifically β-CD and hydroxypropyl-β-cyclodextrin (Hβ-CD), to enhance the solubility and antiviral activity of NTX. Results: The formation of the β-CD:NTX in an aqueous solution was verified using UV–visible spectroscopy, confirming a 1:1 inclusion complex. Characterization of the solid β-CD:NTX complexes was confirmed via FTIR, X-ray diffraction (XRD), scanning electron microscopy (SEM), and DSC-TGA analyses. Molecular docking studies revealed that the NTX thiazole ring with the nitro group was positioned within the β-CDs cavity, while the benzene ring remained outside. Phase solubility tests showed that β-CD:NTX complexes were formed with high stability constants, demonstrating a linear increase in NTX solubility as the β-CD concentration increased. Dissolution tests revealed rapid and nearly complete NTX release within 90 min for β-CD:NTX and Hβ-CD:NTX complexes. The β-CD:NTX complexes were tested for their antiviral activity against Herpes simplex virus (HSV-1) cultures. Results showed that the Hβ-CD:NTX complex had significantly higher antiviral efficacy than β-CD:NTX and free NTX alone. Moreover, cytotoxicity and cellular uptake studies on Vero cells indicated that the Hβ-CD:NTX complex demonstrated lower cytotoxicity and had the highest IC₅₀ value, followed by β-CD:NTX and free NTX. Conclusions: These findings suggest that Hβ-CD:NTX inclusion complexes may serve as effective carriers for delivering NTX in HSV-1 treatments using Vero cell models. Full article

Background: Nabumetone (NAB) is a poorly soluble nonsteroidal anti-inflammatory prodrug (BCS class II drug) whose solubility is significantly improved by complexation with cyclodextrins (CDs). Methods: The solid complexes, in a 1:1 molar ratio, were prepared by mechanochemical activation by grinding, using β-cyclodextrin (β-CD) and its derivatives, hydroxypropyl- and sulfobutylether-β-cyclodextrin (HP-β-CD and SBE-β-CD). The complexation was confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and attenuated total reflectance Fourier-transformed infrared spectroscopy (ATR–FTIR). Obtained products were further characterized regarding their solubility, in vitro dissolution, permeability and chemical stability. Results: Co-grinding with HP-β-CD and SBE-β-CD yielded products that showed in vitro dissolution profiles in hydrochloric acid medium (pH 1.2) that were substantially different from that of pure NAB, yielding dissolution efficiency enhancements of 34.86 ± 1.64 and 58.30 ± 0.28 times, respectively, for the optimized products. Their in vitro dissolution and gastrointestinal permeability were also studied in a low-volume environment at pH 6.8, corresponding to the intestinal environment. Both β-CD derivatives increased NAB dissolution rate and NAB mass transport across the biomimetic membrane. The effect of β-CD derivatives on NAB chemical stability was studied under the stress conditions by the developed and validated UHPLC–DAD–HRMS method. In acidic conditions, pure and complexed NAB was prone to hydrolytic degradation, yielding one degradation product—pharmacologically inactive NAB metabolite. However, under the oxidative conditions at elevated temperatures, 10 NAB degradation products were identified from co-ground samples. All systems were stable during photo- and long-term stability studies. Conclusions: NAB complexes with HP-β-CD and SBE-β-CD are promising candidates for pharmaceutical product development. Full article

Four cyclodextrins (CDs) including heptakis-O-(2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), heptakis-O-(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), β-cyclodextrin (β-CD), and γ-cyclodextrin (γ-CD) were evaluated for their ability to enhance the aqueous solubility of kaempferol (Kae). Phase solubility studies indicated that these four CDs can form 1:1 type complexes with Kae and that HP-β-CD demonstrated the most significant solubilizing effect on Kae. Among the CDs tested, HP-β-CD demonstrated the most significant solubilizing effect on Kae. With an HP-β-CD concentration of 5.00 × 10⁻³ mol·L⁻¹, the concentration of Kae reached 4.56 × 10⁻⁵ mol·L⁻¹, which is 12.7 times greater than its solubility in water. Characterization of the HP-β-CD/Kae complex was performed using empirical methods. Molecular docking indicated that the A and C rings of Kae fit into the hydrophobic cavity of HP-β-CD, while the B ring remained at the rim. Six hydrogen bonds were found between HP-β-CD and the -OH groups of Kae. The negative complexation energy (ΔE) suggests the complex formation was exergonic. A 30-ns molecular dynamics simulation revealed no significant structural changes, with average root-mean-square deviation RMSD values of 2.230 Å for HP-β-CD and 0.786 Å for Kae, indicating high stability of the complex. Full article

During aging, disruptions in various signaling pathways become more common. Some older patients will exhibit irregular bone morphogenetic protein (BMP) signaling, which can lead to osteoporosis (OP)—a debilitating bone disease resulting from an imbalance between osteoblasts and osteoclasts. In 2002, the Food and Drug Administration (FDA) approved recombinant human BMP-2 (rhBMP-2) for use in spinal fusion surgeries as it is required for bone formation. However, complications with rhBMP-2 arose and primary osteoblasts from OP patients often fail to respond to BMP-2. Although patient samples are available for study, previous medical histories can impact results. Consequently, the C57BL/6 mouse line serves as a valuable model for studying OP and aging. We find that BMP receptor type Ia (BMPRIa) is upregulated in the bone marrow stromal cells (BMSCs) of 15-month-old mice, consistent with prior data. Furthermore, conjugating BMP-2 with Quantum Dots (QDot^®s) allows effective binding to BMPRIa, creating a fluorescent tag for BMP-2. Furthermore, after treating BMSCs with methyl-β-cyclodextrin (MβCD), a disruptor of cellular endocytosis, BMP signaling is restored in 15-month-old mice, as shown by von Kossa assays. MβCD has the potential to restore BMPRIa function, and the BMP signaling pathway offers a promising avenue for future OP therapies. Full article

Background/Objectives: The work investigates the effect of the estragole complex encapsulated in beta-cyclodextrin (ES/β-CD) in modulating bacterial resistance, specifically in Staphylococcus aureus strains expressing NorA and MepA efflux pumps. Efflux pumps are mechanisms that bacteria use to resist antibiotics by expelling them from the cell. Methodology: Several compounds and antibiotics, such as ciprofloxacin and norfloxacin, were used to evaluate the antimicrobial activity and the ability of the ES/β-CD complex to reverse resistance. Methods: The study included scanning electron microscopy assays, minimum inhibitory concentration (MIC) determination, and efflux pump inhibition tests. Results: The ES/β-CD complex did not show significant direct antibacterial activity. However, it modulated the action of norfloxacin, decreasing the MIC when combined with this antibiotic in the 1199B (NorA) strain. These results suggest a potential for synergy but not a direct inhibition of efflux pumps. Conclusion: ES/β-CD can potentiate the efficacy of some antibiotics but does not directly act as an efflux pump inhibitor; it is more of an antibiotic potentiator than a direct solution to bacterial resistance. The molecular docking simulation data suggest its high affinity for forming the ES/β-CD complex. The pharmacokinetic predictions based on MPO suggest that the compound has moderate lipophilicity, highly effective cellular permeability, and low incidence of organic toxicity, pointing to a promising pharmacological principle with controlled daily oral dosing. Conclusions: These results indicate this complex’s possible and relevant association as an adjuvant in antibiotic therapy to reduce multidrug-resistant bacteria; however, new in vivo assays are necessary to confirm this effect. Full article

Heavy metal ions in industrial wastewater pose significant environmental and ecological threats. In this work, a hydrogel featuring a double network structure was synthesized via radical polymerization and cross-linking of β-cyclodextrin (CD) and carboxymethylcellulose (CMC) with acrylic acid (AA). The hydrogel’s functional groups and microstructure were characterized using Fourier transform infrared spectroscopy (FTIR-ATR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). Mechanical properties were evaluated through rheological and compression tests. The study examined the impact of initial metal ion concentration, adsorbent-ion contact time, and solution pH on adsorption capacity. The maximum adsorption capacities of the functionalized CD/CMC-PAA-MBA hydrogel for Cu²⁺, Pb²⁺, and Cd²⁺ ions were 158.12, 393.56, and 290.12 mg/g, respectively. Notably, the hydrogel exhibited the highest selectivity for Pb²⁺ in mixed solutions. The adsorption kinetics of the metal ions were modeled using the pseudo-second-order rate equation and the Langmuir adsorption isotherm. Full article

Mycoplasma bovis (M. bovis) is capable of causing pneumonia, arthritis, mastitis, and various other ailments in cattle of all age groups, posing a significant threat to the healthy progression of the worldwide cattle industry. The invasion of non-phagocytic host cells serves as a pivotal mechanism enabling M. bovis to evade the immune system and penetrate mucosal barriers, thereby promoting its spread. To investigate the differences in M. bovis invasion into four types of non-phagocytic cells (Madin–Darby bovine kidney (MDBK) cells, embryonic bovine lung (EBL) cells, bovine embryo tracheal (EBTr) cells and bovine turbinate (BT) cells) and further elucidate its invasion mechanism, this study first optimized the experimental methods for M. bovis invasion into cells. Utilizing laser scanning confocal microscopy, transmission electron microscopy, and high-content live-cell imaging systems, the invasion process of M. bovis into four types of non-phagocytic cells was observed. The invasion rates of three different strains of M. bovis (PG45, 07801, 08M) were quantified through the plate counting method. In order to clarify the specific pathway of M. bovis invasion into cells, chlorpromazine (CPZ), amiloride (AMI), and methyl-β-cyclodextrin (M-β-CD) were used to inhibit CLR-mediated clathrin-dependent endocytosis (CDE) pathway, macropinocytosis, and lipid raft pathway, respectively. Subsequently, the invasion rates of PG45 into these four types of cells were measured. Using siRNA technology, the expression of clathrin (CLR) in EBL cells was knocked down to further verify the role of CLR in the invasion process of M. bovis. The results showed that the optimal conditions for M. bovis to invade non-phagocytic cells were a multiplicity of infection (MOI) of 1000 and an optimal invasion time of 4 h. All three strains of M. bovis have the ability to invade the four types of non-phagocytic cells, yet their invasion abilities vary significantly. Observations from transmission electron microscopy further confirmed that at 120 min post-infection, PG45 had successfully invaded EBL cells and was present within endocytic vesicles. It is noteworthy that almost all PG45 successfully escaped from the endocytic vesicles after 240 min of infection had passed. Through chemical inhibition experiments and CLR protein knockdown experiments, it was found that when the CDE and lipid raft pathways were blocked or CLR protein expression was reduced, the invasion rates of PG45, 07801, and 08M in MDBK, EBL, EBTr, and BT cells were significantly decreased (p < 0.05). The above results indicate that M. bovis can invade all types of non-phagocytic cells through endocytic pathways involving CDE (clathrin-dependent endocytosis) or lipid raft-mediated endocytosis, and possesses the ability to escape from phagosomes. Full article

The most important issues in acute myeloid leukemia are preventing relapse and treating relapse. Although the remission rate has improved to approximately 80%, the 5-year survival rate is only around 30%. The main reasons for this are the high relapse rate and the limited treatment options. In chronic myeloid leukemia patients, when a deep molecular response is achieved for a certain period of time through tyrosine kinase inhibitor treatment, about half of them will reach treatment-free remission, but relapse is still a problem. Therefore, potential therapeutic targets for myeloid leukemias are eagerly awaited. Autophagy suppresses the development of cancer by maintaining cellular homeostasis; however, it also promotes cancer progression by helping cancer cells survive under various metabolic stresses. In addition, autophagy is promoted or suppressed in cancer cells by various genetic mutations. Therefore, the development of therapies that target autophagy is also being actively researched in the field of leukemia. In this review, studies of the role of autophagy in hematopoiesis, leukemogenesis, and myeloid leukemias are presented, and the impact of autophagy regulation on leukemia treatment and the clinical trials of autophagy-related drugs to date is discussed. Full article

Chronic pain (CP), including pain related to cancer, affects approximately 2 billion people worldwide, significantly diminishing quality of life and imposing socio-economic burdens. Current treatments often provide limited relief and may cause adverse effects, demanding more effective alternatives. Natural compounds from Cannabis sativa L., particularly cannabinoids like THC and CBD, exhibit analgesic and anti-inflammatory properties, but their therapeutic use is restricted by poor solubility and low bioavailability. Cyclodextrins (CDs) and cyclic oligosaccharides may encapsulate hydrophobic drugs in order to enhance their solubility and stability, offering a promising solution to these challenges. This study explores the formation of CD inclusion complexes with cannabinoids and specific terpenes, such as D-limonene (LIM), beta-caryophyllene (BCP), and gamma-terpinene (γ-TPN), aiming to improve pharmacokinetic profiles and therapeutic efficacy. We discuss analytical techniques for characterizing these complexes and their mechanisms of action, highlighting the potential of CDs to optimize drug formulations. The integration of CDs in cannabinoid therapies may enhance patient compliance and treatment outcomes in CP management. Future research should focus on innovative formulations and delivery systems to maximize the clinical applications of those compounds. Full article

Cyclodextrins (CDs) have garnered significant attention in various scientific and industrial fields due to their unique ability to form inclusion complexes with a wide range of guest molecules. This review comprehensively explores the latest advancements in cyclodextrin chemistry, focusing on the synthesis and characterization of cyclodextrin derivatives and their inclusion complexes. This review examines the biological activities of cyclodextrins, highlighting their pharmacological properties and pharmacokinetics, and discussing their promising applications in drug delivery systems. Furthermore, the industrial utilization of cyclodextrins, including their role in nanomaterials and nanostructured coatings, as well as their potential in environmental remediation, are explored. The present research also addresses the critical aspect of toxicity, particularly concerning cyclodextrin inclusion complexes, providing an overview of the current understanding and safety considerations. Through a multidisciplinary approach, the aim is to present a complete view of cyclodextrins, underscoring their versatility and impact across various domains. Full article

The modulation of the gut microbiome through dietary components has garnered significant attention for its potential health benefits. Prebiotics, non-digestible food ingredients that promote the growth of beneficial gut bacteria, play a crucial role in maintaining gut health, enhancing immune function, and potentially preventing various metabolic and inflammatory disorders. This review explores the prebiotic activity of cyclodextrins and dextrans, focusing on their ability to influence gut microbiota composition and function. Both cyclodextrins and dextrans have demonstrated the capacity to promote the growth of beneficial bacterial populations, while also impacting short-chain fatty acid production, crucial for gut health. Full article

Mitragynine is an “atypic opioid” analgesic with an alternative mechanism of action and a favorable side-effect profile. Our aim was to optimize the alkaloid extraction procedure from kratom leaves and to determine and isolate the most relevant compounds capable of penetrating the central nervous system. The PAMPA-BBB study revealed that mitragynine and its coalkaloids, speciociliatine, speciogynine, and paynantheine, possess excellent in vitro BBB permeability. An optimized sequence of CPC, flash chromatography, and preparative HPLC methods was used to isolate the four identified BBB+ alkaloids. To improve the bioavailability of the isolated alkaloids, their cyclodextrin (CD) complexation behavior was investigated via affinity capillary electrophoresis using almost 40 CD derivatives. The apparent alkaloid–CD complex stability constants were determined and compared, and the most relevant CDs phase-solubility studies were also performed. Both the neutral and negatively charged derivatives were able to form complexes with all four kratom alkaloids. It was found that cavity size, substituent type, and degree of substitution also influenced complex formation. The negatively charged Sugammadex, Subetadex, and the sufoalkylated-beta-CD analogs were able to form the most stable complexes, exceeding 1000 M⁻¹. These results serve as a good basis for further solubility and stability enhancement studies of kratom alkaloids. Full article

We reported the gold/silver core-shell nanoparticles (Au_core@Ag_shell NPs) functionalized with β-cyclodextrin (β-CD) as versatile nano-agents demonstrated for human urine-based biosensing of cysteamine and catalytic conversion from nitrobenzene (NB) to aniline. First, the hybrid bimetallic nanoparticles, i.e., β-CD-Au_core@Ag_shell NPs, constituted a colorimetric sensing platform based on localized surface plasmons, enabling cysteamine (Cyst) to be detected in a remarkably rapid manner, i.e., within 2 min, which was greatly shortened in comparison with that of our previous report. This was due largely to use of β-CD being effectively replaceable by Cyst. The detection of Cyst was demonstrated using human urine specimens in the linear range of 25–750 nM with a limit of detection of 1.83 nM. Excellent specificity in detecting Cyst was also demonstrated against potential interfering molecules. Meanwhile, the β-CD-Au_core@Ag_shell NPs were demonstrated as nanocatalysts for converting NB to aniline with efficiency enhanced by more than three-fold over the pure gold nanoparticles previously reported, due to the dual functions of the structural core-shell. The demonstrated versatile features of the hybrid nanoparticles can find applications in human urine-based biosensors for Cyst detection, and in the screening of Cyst-containing drugs, while detoxicating NB for ecological protection in aqueous media. Full article

The contamination of the natural environment by xenobiotics and emerging contaminants, including pharmaceuticals, poses significant risks to ecosystems and human health. Among these contaminants, hormones and pharmaceutical compounds are particularly concerning due to their persistence and potential biological effects even at low concentrations. In this study, we investigated the efficacy of poly-amino-β-cyclodextrin (PA-β-CD) microparticles in adsorbing and reducing specific xenobiotics and pharmaceuticals from aqueous solutions. Our research focused on four contaminants: two hormones, testosterone and progesterone, and two pharmaceutical drugs, diclofenac and carbamazepine. High-performance liquid chromatography (HPLC) was employed to quantify the adsorption capacity and efficiency of PA-β-CD microparticles. Full article