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Computational Biology and Chemistry Aug 2024Trastuzumab resistance presents a significant challenge in the treatment of HER2+ breast cancer, necessitating the investigation of combination therapies to overcome...
Bioinformatics and In Vitro Study Reveal ERα as The Potential Target Gene of Honokiol to Enhance Trastuzumab Sensitivity in HER2+ Trastuzumab-Resistant Breast Cancer Cells.
Trastuzumab resistance presents a significant challenge in the treatment of HER2+ breast cancer, necessitating the investigation of combination therapies to overcome this resistance. Honokiol, a compound with broad anticancer activity, has shown promise in this regard. This study aims to discover the effect of honokiol in increasing trastuzumab sensitivity in HER2+ trastuzumab-resistant breast cancer cells HCC1954 and the underline mechanisms behind. A bioinformatics study performed to explore the most potential target hub gene for honokiol in HER2+ breast cancer. Honokiol, trastuzumab and combined treatment cytotoxicity activity was then evaluated in both parental HCC1954 and trastuzumab resistance (TR-HCC1954) cells using MTT assay. The expression levels of these hub genes were then analyzed using qRT-PCR and those that could not be analyzed were subjected to molecular docking to determine their potential. Honokiol showed a potent cytotoxicity activity with an IC of 41.05 μM and 69.61 μM in parental HCC1954 and TR-HCC1954 cell line respectively. Furthermore, the combination of honokiol and trastuzumab resulted in significant differences in cytotoxicity in TR-HCC1954 cells at specific concentrations. Molecular docking and the qRT-PCR showed that the potential ERα identified from the bioinformatics analysis was affected by the treatment. Our results show that honokiol has the potential to increase the sensitivity of trastuzumab in HER2+ trastuzumab resistant breast cancer cell line HCC1954 by affecting regulating estrogen receptor signaling. Further research is necessary to validate these findings.
Topics: Humans; Trastuzumab; Biphenyl Compounds; Lignans; Breast Neoplasms; Drug Resistance, Neoplasm; Estrogen Receptor alpha; Receptor, ErbB-2; Computational Biology; Female; Molecular Docking Simulation; Drug Screening Assays, Antitumor; Cell Proliferation; Cell Line, Tumor; Antineoplastic Agents; Dose-Response Relationship, Drug; Cell Survival; Allyl Compounds; Phenols
PubMed: 38805864
DOI: 10.1016/j.compbiolchem.2024.108084 -
The Journal of Organic Chemistry Jun 2024Trace palladium in synthetic materials can be rapidly and inexpensively semiquantified by a catalysis-based fluorometric method that converts resorufin allyl ether to...
Trace palladium in synthetic materials can be rapidly and inexpensively semiquantified by a catalysis-based fluorometric method that converts resorufin allyl ether to resorufin. However, whether sulfur compounds would interfere with this method has not been systematically studied. Herein, we show that although thiourea in solution interferes with quantification, sulfide, thiol, and thiocarbamate do not. The fluorometric method can also detect palladium bound to sulfur-based scavenger resin and outperform inductively coupled plasma mass spectrometry for detecting trace palladium in ibuprofen.
Topics: Palladium; Ibuprofen; Catalysis; Fluorometry; Molecular Structure; Sulfur Compounds
PubMed: 38804706
DOI: 10.1021/acs.joc.4c00651 -
International Journal of Biological... Jun 2024This study investigated the release of aromatic compounds with distinct functional groups within bilayer microcapsules. Bilayer microcapsules of four distinctive core...
This study investigated the release of aromatic compounds with distinct functional groups within bilayer microcapsules. Bilayer microcapsules of four distinctive core materials (benzyl alcohol, eugenol, cinnamaldehyde, and benzoic acid) were synthesized via freeze-drying. Chitosan (CS) and sodium alginate (ALG) were used as wall materials. CS concentration, using orthogonal experiments with the loading ratio as a metric. Under optimal conditions, three other types of microcapsules (cinnamic aldehyde, benzoic acid, and benzyl alcohol) were obtained. The four types of microcapsules were characterized using Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), and thermogravimetric analysis (TGA), and their sustained release characteristics were evaluated. The optimal conditions were: CS dosage, 1.2 %; CS-to-eugenol mass ratio, 1:2; and CS-to-ALG mass ratio, 1:1. By comparing the IR spectra of the four types of microcapsules, wall material, and core material, the core materials were revealed to be encapsulated within the wall material. SEM results revealed that the granular protuberances on the surface of the microcapsules were closely aligned and persistent when magnified 2000×. The TEM results indicated that all four microcapsules had a spherical and bilayer structure. The thermal stability and sustained release results showed that the four microcapsules were more resilient and less volatile than the four core materials. The release conformed to first-order kinetics, and the release ratios of the four microcapsules were as follows: benzyl alcohol microcapsules ˃ eugenol microcapsules ˃ cinnamaldehyde microcapsules ˃ benzoic acid microcapsules. The prepared bilayer microcapsules encapsulated four different core materials with good sustained release properties.
Topics: Chitosan; Capsules; Alginates; Delayed-Action Preparations; Drug Liberation; Eugenol; Benzoic Acid; Spectroscopy, Fourier Transform Infrared; Acrolein; Drug Carriers; Thermogravimetry
PubMed: 38797291
DOI: 10.1016/j.ijbiomac.2024.132663 -
International Journal of Biological... Jun 2024The amelioration of refractory diabetic ulcers presents a formidable conundrum on a global scale, attributable to the elevated peril of contagion and protracted...
The amelioration of refractory diabetic ulcers presents a formidable conundrum on a global scale, attributable to the elevated peril of contagion and protracted convalescence durations. Within the purlieus of this reparative epoch, the deployment of efficacious wound coverings endowed with both angiogenesis and antibacterial attributes is of paramount significance. Hydrogel wound dressings are distinguished by their elevated biocompatibility, adhesive tenacity, and innate regenerative capacity. Eugenol, a substance distilled from the blossoms of the lilac, serves as a precursor to metformin and is known to impede the genesis of reactive oxygen species. Although its antibacterial effects have been extensively chronicled, the angiogenic ramifications of eugenol within the context of wound remediation remain under-investigated. This research aimed to evaluate the effectiveness of eugenol-infused hydrogel as a wound dressing material. In this context, polyurethane gelatin (PG) was combined with eugenol at concentrations of 0.5% and 1%, creating PG-eugenol hydrogel mixtures with specific mass ratios for both in vivo and in vitro assessments. The in vivo studies indicated that hydrogels infused with eugenol expedited diabetic wound healing by fostering angiogenesis. Enhanced healing was noted, attributed to improved antibacterial and angiogenic properties, increased cell proliferation, tissue regeneration, and re-epithelialization. The in vitro analyses revealed that eugenol-enriched hydrogels stimulated the growth of fibroblasts (HFF-1) and human umbilical vein endothelial cells (HUVECs) and exhibited antibacterial characteristics. This investigation confirms the potential of eugenol-laden hydrogels in effectively treating diabetic wound defects.
Topics: Eugenol; Wound Healing; Polyurethanes; Anti-Bacterial Agents; Gelatin; Animals; Neovascularization, Physiologic; Bandages; Rats; Hydrogels; Male; Humans; Diabetes Mellitus, Experimental; Cell Proliferation; Human Umbilical Vein Endothelial Cells; Angiogenesis
PubMed: 38795896
DOI: 10.1016/j.ijbiomac.2024.132619 -
International Journal of Molecular... May 2024is a species of tick in the family Ixodidae, with equids and capybaras among its preferred hosts. In this study, the acaricidal activity of the essential oil (EO) from...
is a species of tick in the family Ixodidae, with equids and capybaras among its preferred hosts. In this study, the acaricidal activity of the essential oil (EO) from and its main component, Dillapiole, were evaluated against larvae of to establish lethal concentration values and assess the effects of these compounds on tick enzymes. Dillapiole exhibited slightly greater activity (LC = 3.38 mg/mL; 95% CI = 3.24 to 3.54) than EO (LC = 3.49 mg/mL; 95% CI = 3.36 to 3.62) against ticks. The activities of α-esterase (α-EST), β-esterase (β-EST), and glutathione-S-transferase (GST) enzymes in larvae treated with Dillapiole showed a significant increase compared to the control at all concentrations (LC, LC, LC and LC), similar results were obtained with EO, except for α-EST, which did not differ from the control at the highest concentration (LC). The results of the acetylcholinesterase (AChE) activity show an increase in enzyme activity at the two lower concentrations (LC and LC) and a reduction in activity at the two higher, lethal concentrations (LC and LC) compared to the control. These results suggest potential mechanisms of action for these natural acaricides and can provide guidance for the future development of potential plant-derived formulations.
Topics: Animals; Oils, Volatile; Acetylcholinesterase; Piper; Larva; Acaricides; Glutathione Transferase; Amblyomma; Inactivation, Metabolic; Cholinesterase Inhibitors; Benzodioxoles; Esterases; Allyl Compounds; Dioxoles
PubMed: 38791458
DOI: 10.3390/ijms25105420 -
European Journal of Pharmaceutics and... Jul 2024Orodispersible films (ODFs) have emerged as an advanced and patient-friendly delivery system due to ease of administration, improved patient compliance, quick release...
Orodispersible films (ODFs) have emerged as an advanced and patient-friendly delivery system due to ease of administration, improved patient compliance, quick release and taste-masking of active pharmaceutical ingredients. This research reports the preparation of the ODF containing eugenol and borax (EB-ODF) by a solvent casting technique for treating mouth ulcers. The EB-ODF consisted of vinyl pyrrolidone/vinyl acetate copolymer (Kollidon® VA64, VA64) and hydroxypropyl methylcellulose (HPMC-K250) as the film formers where eugenol and borax were loaded. The thickness of the EB-ODF obtained was 0.119 ± 0.001 mm and the tensile strength was 13.1 ± 1.1 N/mm (p > 0.05). The prepared films disintegrated in the oral cavity within 30 s and over 90% of the eugenol was released from the film in the first 5 min. Furthermore, the combined application of eugenol and borax, loaded in EB-ODF, displayed notable synergetic antibacterial property against both gram-negative and gram-positive bacteria. In an in-vivo study on a rat model with chemical burn-induced oral ulcers, the EB-ODF treatment group had a 100% reduction in ulcer area (p > 0.05) after 10 days of treatment and demonstrated a 38.7% higher reduction in oral ulcer area compared to the Dingpeng Cream treatment group (p < 0.0001). The EB-ODF treatment group showed minimal oral irritation, scoring only 1 point and a 65% preference in the taste tests (p < 0.0001). In summary, EB-ODF had successfully overcome the poor palatability of commercially available formulation and provided notable potential for further ulcer treatment product development.
Topics: Eugenol; Animals; Rats; Borates; Oral Ulcer; Male; Administration, Oral; Drug Delivery Systems; Drug Liberation; Hypromellose Derivatives; Rats, Wistar; Tensile Strength
PubMed: 38789062
DOI: 10.1016/j.ejpb.2024.114337 -
Chemistry (Weinheim An Der Bergstrasse,... May 2024Borane catalysis has emerged as a powerful technology in epoxide polymerization. Still, the structure-activity correlations for these catalysts are not fully understood...
Borane catalysis has emerged as a powerful technology in epoxide polymerization. Still, the structure-activity correlations for these catalysts are not fully understood to date, especially regarding compounds with nonionic backbones. Thus, in this work, 13 different borane catalysts of this respective type are described and investigated for their epoxide oligomerization and polymerization performance, using propylene oxide (PO), 1-butylene oxide (BO) and allyl glycidyl ether (AGE) as monomers. Structurally, special emphasis is put on catalysts with different linker lengths and linker flexibilities as well as the introduction of more than two borane functionalities. Importantly, this screening is conducted both under typical polymerization conditions as well as under the chain transfer agent (CTA)-rich conditions relevant for large-scale production. It is found that suitable preorganization of the borane groups, such as present in biphenyl derivatives, offers a simple route to high-performing catalysts and quantitative monomer conversion of the investigated epoxides. Furthermore, it is demonstrated that a diborane-catalyzed oligomerization can be kept active over weeks, whereby repeated addition of monomer batches (14 steps) constantly results in full conversion and well-defined oligoethers, underlining the practical potential of this method. The absence of co-initiating counter ions is suggested as an inherent advantage of nonionic catalysts.
PubMed: 38785225
DOI: 10.1002/chem.202401268 -
Journal of Biochemical and Molecular... Jun 2024The current study was focused on the anticancer activity of myristicin against MCF-7 human breast cancer (BC) cells. BC is the most common and leading malignant disease...
The current study was focused on the anticancer activity of myristicin against MCF-7 human breast cancer (BC) cells. BC is the most common and leading malignant disease in women worldwide. Now-a-days, various conventional therapies are used against BC and still represent a chief challenge because those treatments fail to differentiate normal cells from malignant cells, and they have severe side effects also. So, there is a need develop new therapies to decrease BC-related morbidity and mortality. Myristicin, a 1‑allyl‑5‑methoxy‑3, 4‑methylenedioxybenzene, is a main active aromatic compound present in various spices, such as nutmeg, mace, carrot, cinnamon, parsely and some essential oils. Myristicin has a wide range of effects, including antitumor, antioxidative and antimicrobial activity. Nevertheless, the effects of myristicin on human BC cells remain largely unrevealed. The cytotoxicity effect of myristicin on MCF‑7 cells was increased dose dependently detected by (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Lactate Dehydrogenase assays. Myristicin was found to be significantly inducing the cell apoptosis, as compared to control, using acridine orange/ethidium bromide, Hoechst stain and annexin V. Moreover, it activates cell antimigration, intracellular reactive oxygen species generation and cell cycle arrest in the G/S phase. In addition, myristicin induces the expression of apoptosis and cell cycle genes (Caspases8, Bax, Bid, Bcl2, PARP, p53, and Cdk1) was demonstrated by quantitative polymerase chain reaction and apoptosis proteins (c-PARP, Caspase 9, Cytochrome C, PDI) expression was also analyzed with western blot. Overall, we illustrated that myristicin could regulate apoptosis signaling pathways in MCF-7 BC cells.
Topics: Humans; Apoptosis; MCF-7 Cells; Breast Neoplasms; Female; Dioxolanes; Benzyl Compounds; Allylbenzene Derivatives; Cell Cycle Checkpoints; Reactive Oxygen Species
PubMed: 38779996
DOI: 10.1002/jbt.23740 -
Nature Communications May 2024Transition-metal catalyzed allylic substitution reactions of alkenes are among the most efficient methods for synthesizing diene compounds, driven by the inherent...
Transition-metal catalyzed allylic substitution reactions of alkenes are among the most efficient methods for synthesizing diene compounds, driven by the inherent preference for an inner-sphere mechanism. Here, we present a demonstration of an outer-sphere mechanism in Rh-catalyzed allylic substitution reaction of simple alkenes using gem-difluorinated cyclopropanes as allyl surrogates. This unconventional mechanism offers an opportunity for the fluorine recycling of gem-difluorinated cyclopropanes via C - F bond cleavage/reformation, ultimately delivering allylic carbofluorination products. The developed method tolerates a wide range of simple alkenes, providing access to secondary, tertiary fluorides and gem-difluorides with 100% atom economy. DFT calculations reveal that the C - C bond formation goes through an unusual outer-sphere nucleophilic substitution of the alkenes to the allyl-Rh species instead of migration insertion, and the generated carbon cation then forms the C - F bond with tetrafluoroborate as a fluoride shuttle.
PubMed: 38773086
DOI: 10.1038/s41467-024-48541-5 -
Poultry Science Jul 2024This study was designed to examine the impact of aspirin eugenol ester (AEE) on the growth performance, serum antioxidant capacity, jejunal barrier function, and cecal...
Effect of dietary aspirin eugenol ester on the growth performance, antioxidant capacity, intestinal inflammation, and cecal microbiota of broilers under high stocking density.
This study was designed to examine the impact of aspirin eugenol ester (AEE) on the growth performance, serum antioxidant capacity, jejunal barrier function, and cecal microbiota of broilers raised under stressful high density (HD) stocking conditions compared with normal density broilers (ND). A total of 432 one-day-old AA+ male broilers were randomly divided into 4 groups: normal density (ND, 14 broilers /m), high density (HD, 22 broilers /m), ND + AEE, and HD + AEE. The results of the study revealed a significant decrease in the growth performance of broiler chickens as a result of HD stress (P < 0.05). The total antioxidant capacity (T-AOC) in serum demonstrated a significant decrease (P < 0.05) at both 28 and 35 d. Conversely, the serum level of malondialdehyde (MDA) exhibited a significant increase (P < 0.05). Dietary supplementation of AEE resulted in a significant elevation (P < 0.05) of serum GSH-PX, SOD and T-AOC activity at both 28 and 35 d. Moreover, exposure to HD stress resulted in a considerable reduction in the height of intestinal villi and mRNA expression of tight junction proteins in the jejunum, along with, a significant elevation in the mRNA expression of inflammatory cytokines (P < 0.05). However, the administration of AEE reversed the adverse effects of HD-induced stress on villus height and suppressed the mRNA expression of the pro-inflammatory genes, COX-2 and mPGES-1. Additionally, the exposure to HD stress resulted in a substantial reduction in the α-diversity of cecal microbiota and disruption in the equilibrium of intestinal microbial composition, with a notable decrease in the relative abundance of Bacteroides and Faecalibacterium (P < 0.05). In contrast, the addition of AEE to the feed resulted in a notable increase in the relative abundance of Phascolarctobacterium and enhanced microbial diversity (P < 0.05). The inclusion of AEE in the diet has been demonstrated to enhance intestinal integrity and growth performance of broilers by effectively mitigating disruptions in gut microbiota induced by HD stress.
Topics: Animals; Chickens; Male; Gastrointestinal Microbiome; Antioxidants; Diet; Cecum; Aspirin; Animal Feed; Dietary Supplements; Eugenol; Random Allocation; Animal Husbandry; Inflammation
PubMed: 38772090
DOI: 10.1016/j.psj.2024.103825