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Nasal systemic drug delivery may provide an easy way to substitute parenteral or oral dosing, however, the excipients have an important role in nasal formulations to increase the permeability of the mucosa and prolong the residence time of the drug. In this work, we aimed to produce meloxicam potassium monohydrate (MXP) containing nasal powders by a nano spray drier with the use of a neutral, an anionic and a cationic ß-cyclodextrin as permeation enhancers, and (polyvinyl)alcohol (PVA) as a water soluble polymer. The following examinations were performed in order to study the effect of the applied excipients on the nasal applicability of the formulations: laser scattering, scanning electron microscope measurement, XRPD, DSC and FTIR measurements, adhesivity, in vitro drug release and permeability tests through an artificial membrane and RPMI 2650 cells. Based on our results, spherical particles were prepared with a size of 1.89-2.21 µm in which MXP was present in an amorphous state. Secondary interactions were formed between the excipients and the drug. The charged cyclodextrin-based formulations showed significantly higher adhesive force values regardless of the presence of PVA. The drug release was fast and complete. The passive diffusion of MXP was influenced not only by the charge of the cyclodextrin, but the presence of PVA, too. The permeation of the drug was enhanced in the presence of the anionic cyclodextrin testing it on RPMI 2650 cell model.
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5-Hydroxytryptophan (5-HTP), a precursor of the neurotransmitter serotonin in mammals, has demonstrated efficacy in treating various diseases such as depression, fibromyalgia and obesity. However, conventional biosynthesis methods of 5-HTP are limited by low yield and high reagent and process costs. In this study, the strain C1T7-S337A/F318Y with optimized promoter distribution was obtained, and the 5-HTP yield was 60.30â¯% higher than that of the initial strain. An efficient fermentation process for 5-HTP synthesis was developed using strain C1T7-S337A/F318Y with whey powder as a substrate for cell growth and inducer production. Shake flask fermentation experiments yielded 1.302â¯g/L 5-HTP from 2.0â¯g/L L-tryptophan (L-Trp), surpassing the whole-cell biocatalysis by 42.86â¯%. Scale-up to a 5â¯L fermenter further increased the yield to 1.649â¯g/L. This fermentation strategy substantially slashed reagent cost by 95.39â¯%, providing a more economically viable and environmentally sustainable route for industrial biosynthesis of 5-HTP. Moreover, it contributes to the broader utilization of whey powder in various industries.
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5-Hidroxitriptofano , Escherichia coli , Fermentação , Soro do Leite , 5-Hidroxitriptofano/metabolismo , Soro do Leite/metabolismo , Escherichia coli/metabolismo , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Triptofano/metabolismo , Reatores Biológicos/microbiologiaRESUMO
Recently, poultry industry has been seeking antibiotic residue-free poultry products and safe nutritious feed additives. Whether rosemary ultrafine powder (RUP) affects productive performance by regulating the intestinal microbiome of aged layers remains unclear. Here, we investigated the effects of dietary RUP supplementation on the production performance, egg quality, antioxidant capacity, intestinal microbial structure, and metabolome of aged hens. The results indicate that RUP had no significant effect on production performance but significantly enhanced Thick albumen height, Haugh unit, yolk color (P < 0.05), daily feed intake, and qualified egg rate. Serum content of non-esterified fatty acids, catalase, and glutathione peroxidase increased significantly (P < 0.05). Furthermore, the liver total protein content was significantly increased (P < 0.05). 16S rRNA sequence analysis revealed that RUP significantly impacted both α- and ß-diversity of the caecum microbiota. Linear discriminant analysis of effect size and random forest identified Bacteroides, Muribaculum, Butyricimonas, Odoribacter, and Prevotella as biomarkers in groups A and B. In comparing groups A and C, Barnesiella, Turicibacter, and Acholeplasma were critical bacteria, while comparing groups A and D highlighted Barnesiella and Candidatus Saccharimonas as differential bacteria. FAPROTAX analysis of the caecum microbiota revealed that the functional genes associated with harmful substance biodegradation were significantly increased in the RUP-fed group. Based on Spearman correlation analysis, alterations in microbial genera were associated with divergent metabolites. In summary, dietary RUP can improve egg quality and antioxidant capacity and regulate the intestinal microbiome and metabolome in aged breeders. Therefore, RUP can potentially be used as a feed additive to extend breeder service life at an appropriate level of 1.0 g/kg.
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Elderly people avoid eating red meat and dried meat product due to its texture and stiffness; they deprive them of rich sources of nutrients. In addition, food-related diseases are exponentially increasing due to using synthetic additives in food products. Therefore, this research aimed to develop semi-dried goat meat jerky considering geriatric preferences by using natural tenderizers and nitrate. Four treatments were formulated negative control (NC [synthetic nitrite without tenderizers]), positive control (PC [Swiss chard without tenderizers]), T1 (Swiss chard with pineapple powder), and T2 (Swiss chard with pineapple and tomato powder). T1 and T2 had higher processing yield, and rehydration capacity compared with NC and PC. The fat content of T1 and T2 was lower than the control groups. Moisture was significantly higher in T1, NC, and T2 than in PC (p < 0.05). T2 showed the lowest water activity (0.87), lowest shear force (4.82 kgf), and lowest total plate count (TPC). The lowest pH and thiobarbituric acid reactive substances (TBARS) were observed in T1 and T2. T1 showed the lowest lightness and the maximum redness (p < 0.05) while PC showed the lowest yellowness. During the storage period, moisture and pH decreased, and TPC and TBARS significantly increased whereas water activity is stable regardless of the treatment. The results of the myofibrillar fragmentation index (MFI) and sodium dodecyl sulfate-polyacrylamide gel revealed that T1 and T2 more effectively converted protein to polypeptides. In addition, tenderizers positively affected thrombogenicity, atherogenicity, and hypocholesterolemic/hypercholesterolemic indices. T2 observed the highest overall sensory acceptance by reducing goaty flavor. Overall, jerky treated with tenderizers is easily chewable and digestible for the elderly due to its tenderness and essential fatty acids that would be senior-friendly food.
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This study harnessed bivariate correlational analysis, multiple linear regression analysis and tree-based regression analysis to examine the relationship between laser process parameters and the final material properties (bulk density, saturation magnetization (M s ), and coercivity (H c )) of Fe-based nano-crystalline alloys fabricated via laser powder bed fusion (LPBF). A dataset comprising of 162 experimental data points served as the foundation for the investigation. Each data point encompassed five independent variables: laser power (P), laser scan speed (v), hatch spacing (h), layer thickness (t), and energy density (E), along with three dependent variables: bulk density, M s , and H c . The bivariate correlational analysis unveiled that bulk density exhibited a significant correlation with P, v, h, and E, whereas M s and H c displayed significant correlations exclusively with v and P, respectively. This divergence may stem from the strong influence of microstructure on magnetic properties, which can be impacted not only by the laser process parameters explored in this study but also by other factors such as oxygen levels within the build chamber. Furthermore, our statistical analysis revealed that bulk density increased with rising P, h, and E, while decreased with higher v. Regarding the magnetic properties, a high M s was achievable through low v, while low H c resulted from high P. It was concluded that P and v were considered as the primary laser process parameters, influencing h and t due to their control over the melt-pool size. The application of multiple linear regression analysis allowed the prediction of the bulk density by using both laser process parameters and energy density. This approach offered a valuable alternative to time-consuming and costly trial-and-error experiments, yielding a low error of less than 1 % between the mean predicted and experimental values. Although a slightly higher error of approximately 6 % was observed for M s , a clear association was established between M s and v, with lower v values corresponding to higher M s values. Additionally, a further comparison was conducted between multiple linear regression and three tree-based regression models to explore the effectiveness of these approaches.
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Extracellular vesicles (EVs) have emerged as a promising drug delivery system. Connectosomes are a specialized type of EVs that contain connexins in their membranes. Connexin is a surface transmembrane protein that forms connexin hemichannels. When a connexin hemichannel on a connectosome docks with another connexin hemichannel of a target cell, they form a gap junction that allows direct intracellular delivery of therapeutic cargos from within the connectosome to the cytoplasm of the recipient cell. In the present study, we tested the feasibility of converting connectosomes into dry powders by (thin-film) freeze-drying to enable their potential storage in temperatures higher than the recommended -80 °C, while maintaining their activity. Connectosomes were isolated from a genetically engineered HeLa cell line that overexpressing connexin-43 subunit protein tagged with red fluorescence protein. To facilitate the testing of the function of the connectosomes, they were loaded with calcein green dye. Calcein green-loaded connectosomes were thin-film freeze-dried with trehalose alone or trehalose and a polyvinylpyrrolidone polymer as lyoprotectant(s) to produce amorphous powders with high glass transition temperatures (>100 °C). Thin-film freeze-drying did not significantly change the morphology and structure of the connectosomes, nor their particle size distribution. Based on data from confocal microscopy, flow cytometry, and fluorescence spectrometry, the connexin hemichannels in the connectosomes reconstituted from the thin-film freeze-dried powder remained functional, allowing the passage of calcein green through the hemichannels and the release of the calcein green from the connectosomes when the channels were opened by chelating calcium in the reconstituted medium. The function of connectosomes was assessed after one month storage at different temperatures. The connexin hemichannels in connectosomes in liquid lost their function when stored at -19.5 ± 2.2 °C or 6.0 ± 0.5 °C for a month, while those in dry powder form remained functional under the same storage conditions. Finally, using doxorubicin-loaded connectosomes, we showed that the connectosomes reconstituted from thin-film freeze-dried powder remained pharmacologically active. These findings demonstrate that (thin-film) freeze-drying represents a viable method to prepare stable and functional powders of EVs that contain connexins in their membranes.
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Shenling Baizhu Powder (SLBZP), a traditional Chinese medicine (TCM) prescription renowned for its efficacy, is specifically recognized for its therapeutic effects in managing diarrhea associated with spleen qi deficiency. Our previous research has demonstrated that a lard diet in a fatigued state induced diarrhea belonging to spleen qi deficiency in TCM. Through a comprehensive investigation, we aimed to provide insights into the intricate relationship between SLBZP and the modulation of gut microbiota in alleviating symptoms associated with spleen qi deficiency-induced diarrhea. We induced diarrhea in mice by subjecting them to continuous standing on a multiple-platform apparatus while administering lard through intragastric administration for 14 days. Subsequently, we conducted gavage administration of SLBZP at a concentration of 0.637 g/ml for seven days. We observed a therapeutic effect of SLBZP on diarrhea induced by a lard diet in a fatigued state. SLBZP mitigated disorders in lipid metabolism and diminished hepatic oxidative responses. Additionally, SLBZP reversed gut microbiota dysbiosis of diarrheic mice and notably increased the production of short-chain fatty acids (SCFAs), primarily acetic acid, butyric acid, and valeric acid. Through correlation analysis, we additionally identified Lactobacillus reuteri and Lactobacillus intestinalis as potentially pivotal species associated with the therapeutic effects of SLBZP. We demonstrated that SLBZP exerts therapeutic effects on diarrhea caused by a lard diet in a fatigued state by repairing the intestinal mucosal barrier, improving lipid metabolism disorders, and regulating gut microbiota and metabolites SCFAs.
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Background: Atopic dermatitis (AD) is inflammatory disease. So far, therapeutic mechanism of Runfuzhiyang powder on AD remains to be studied. This study aimed to mine key biomarkers to explore potential molecular mechanism for AD incidence and Runfuzhiyang powder treatment. Methods: The control group, AD group, treat group (AD mice treated with Runfuzhiyang powder were utilized for studying. Differentially expressed AD-related genes were acquired by intersecting of key module genes related to control group, AD group and treatment group which were screened by WGCNA and AD-related differentially expressed genes (DEGs). KEGG and GO analyses were further carried out. Next, LASSO regression analysis was utilized to screen feature genes. The ROC curves were applied to validate the diagnostic ability of feature genes to obtain AD-related biomarkers. Then protein-protein interaction (PPI) network, immune infiltration analysis and single-gene gene set enrichment analysis (GSEA) were presented. Finally, TF-mRNA-lncRNA and drug-gene networks of biomarkers were constructed. Results: 4 AD-related biomarkers (Ddit4, Sbf2, Senp8 and Zfp777) were identified in AD groups compared with control group and treat group by LASSO regression analysis. The ROC curves revealed that four biomarkers had good distinguishing ability between AD group and control group, as well as AD group and treatment group. Next, GSEA revealed that pathways of E2F targets, KRAS signaling up and inflammatory response were associated with 4 biomarkers. Then, we found that Ddit4, Sbf2 and Zfp777 were significantly positively correlated with M0 Macrophage, and were significantly negatively relevant to Resting NK. Senp8 was the opposite. Finally, a TF-mRNA-lncRNA network including 200 nodes and 592 edges was generated, and 20 drugs targeting SENP8 were predicted. Conclusion: 4 AD-related and Runfuzhiyang powder treatment-related biomarkers (Ddit4, Sbf2, Senp8 and Zfp777) were identified, which could provide a new idea for targeted treatment and diagnosis of AD.
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A non-invasive capacitance instrument was embedded in the base of a vacuum-drying tray to monitor continuously the residual amount of solvent left in a pharmaceutical powder. Proof of concept was validated with Microcrystalline Cellulose laced with water, as well as water/acetone mixtures absorbed in a spray-dried Copovidone powder. To illustrate the role of impermeability of the base, we derive a model of vapor sorption that reveals the existence of a kinetic limit when solids are thinly spread, and a diffusion limit with greatly diminished effective diffusivity at large powder thickness. By monitoring the residual solvent content of powders, this new in situ technique offers advantages over indirect methods like mass spectrometry of vapor effluents, but without complications associated with probe fouling. To prescribe design guidelines and interpret signals, we model the electric field shed by the probe when a powder holds variable solvent mass fraction in the vertical direction.
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Celulose , Pós , Solventes , Solventes/química , Vácuo , Celulose/química , Celulose/análise , Pirrolidinas/química , Pirrolidinas/análise , Compostos de Vinila/química , Água/química , Dessecação/métodos , Acetona/análise , Acetona/química , Difusão , CinéticaRESUMO
Background: YinChen WuLing Powder (YCWLP) has been recommended by consensus for the treatment of non-alcoholic steatohepatitis (NASH); nevertheless, its specific pharmacological mechanisms remain to be elucidated. This study aims to dissect the mechanisms underlying the therapeutic effects of YCWLP on NASH using a hybrid approach that encompasses network pharmacology, molecular docking, and in vitro experimental validation. Methods: We compiled the chemical constituents of YCWLP from the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform (TCMSP), while potential targets were predicted using the SwissTargetPrediction database. To identify NASH-related candidate targets, comprehensive retrieval was carried out using five authoritative databases. Protein-Protein Interaction (PPI) networks of direct targets of YCWLP in NASH treatment were then constructed using the String database, and functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, were conducted through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Core targets were discerned using the Molecular Complex Detection (MCODE) and cytoHubba algorithms. Subsequently, molecular docking of key compounds to core targets was conducted using AutoDock software. Moreover, we established a free fatty acid-induced HepG2 cell model to simulate NASH in vitro, with YCWLP medicated serum intervention employed to corroborate the network pharmacology-derived hypotheses. Furthermore, a combination of enzyme-linked immunosorbent assay (ELISA), and Western blotting analyses was employed to investigate the lipid, hepatic enzyme, SHP2/PI3K/NLRP3 signaling pathway and associated cytokine levels. Results: The network pharmacology analysis furnished a list of 54 compounds from YCWLP and 167 intersecting targets associated with NASH. Through analytic integration with multiple algorithms, PTPN11 (also known as SHP2) emerged as a core target of YCWLP in mitigating NASH. The in vitro experiments validated that 10% YCWLP medicated serum could remarkably attenuate levels of total cholesterol (TC, 1.25 vs. 3.32) and triglyceride (TG, 0.23 vs. 0.57) while ameliorating alanine aminotransferase (ALT, 7.79 vs. 14.78) and aspartate aminotransferase (AST, 4.64 vs. 8.68) leakage in NASH-afflicted cells. In addition, YCWLP significantly enhanced the phosphorylation of SHP2 (0.55 vs. 0.20) and downregulated the expression of molecules within the SHP2/PI3K/NLRP3 signaling axis, including p-PI3K (0.42 vs. 1.02), NLRP3 (0.47 vs. 0.93), along with downstream effectors-cleaved Caspase-1 (0.21 vs. 0.49), GSDMD-NT (0.24 vs. 0.71), mature interleukin-1ß (IL-1ß, 0.17 vs. 0.48), pro-IL-1ß (0.49 vs. 0.89), mature interleukin-18 (IL-18, 0.15 vs. 0.36), and pro-IL-18 (0.48 vs. 0.95). Conclusion: Our research reveals that YCWLP exerts therapeutic effects against NASH by inhibiting lipid accumulation and inflammation, which involves the attenuation of pyroptosis via the SHP2/PI3K/NLRP3 pathway.
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Recently, deep-red-emitting phosphors that can be excited by ultraviolet (UV) and near-ultraviolet (NUV) light have been extensively investigated for plant growth LED applications. However, due to the harmful effects of these high-energy rays on plants, violet- or blue-excited deep-red-emitting phosphors are considered a more appropriate solution. In this work, SrAl12O19:Cr3+ phosphors were synthesized using a simple solid-state reaction, revealing a strikingly sharp deep-red emission band centered at 694 nm and effective excitation by violet light. The optimal SrAl12O19:1.0%Cr3+ phosphor, annealed at 1500°C, exhibits an extended lifetime of 0.549 ms, an energy activation level of 0.239 eV, a good quantum efficiency (QE) of 36.2%, and superior color purity at 100%. Further, an LED prototype with a precise absorption spectrum for far-red phytochrome (Pfr) has been demonstrated. These results indicate that the synthesized SrAl12O19:1.0%Cr3+ phosphors could be used as a promising deep-red-emitting phosphor for plant growth LED.
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Cromo , Cromo/química , Desenvolvimento Vegetal , Substâncias Luminescentes/química , Substâncias Luminescentes/síntese química , Estrôncio/químicaRESUMO
BACKGROUND: Perioperative bleeding in total hip arthroplasty (THA) can lead to various problems, so effective management of blood loss is needed. This prospective, single-blind, randomized controlled trial aimed to compare the efficacy of topical administration of SURGICEL® (a hemostatic agent of oxidized regenerated cellulose) powder (SP) and tranexamic acid (TXA) in controlling perioperative bleeding during THA. MATERIALS AND METHODS: In total, 114 patients undergoing THA for osteoarthritis were randomized to either group S (THA with SP) or group T (THA with TXA). Data including patient demographics, laboratory data (C-reactive protein [CRP], hemoglobin, and hematocrit), operative time, and intraoperative blood loss were analyzed. Clinical outcomes were assessed using WOMAC, JOA, FJS scores, and visual analog scale (VAS) scores. Primary outcomes were estimated total and postoperative blood loss, while secondary outcomes included hematological test results and various clinical scores. RESULTS: 57 patients were allocated to each group, with 55 in group S and 56 in group T were finally included in the analysis. There was no significant difference (p = 0.141) in estimated total blood loss between group S (788.2 ± 350.1 ml) and group T (714.1 ± 318.4 ml). Hemoglobin and hematocrit levels and WOMAC, and FJS scores were not significantly different between the two groups at any time point. CRP levels were significantly different on postoperative days 4 and 7, and JOA score was significantly different on preoperative and postoperative period. However, the differences in CRP and JOA score values themselves were relatively small and not clinically different. CONCLUSIONS: Topical administration of SP is as effective as TXA in reducing perioperative bleeding in patients undergoing THA. Additionally, no significant difference was observed in early postoperative clinical outcomes between SP and TXA. LEVEL OF EVIDENCE: Therapeutic Level I. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) registration number UMIN000047607.
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The study constructed fingerprints and analyzed adsorption rules of volatile compounds (VOCs) in egg powder (EP) under different production processes, including egg white powder (EWP), egg yolk powder (EYP) and whole egg powder (WEP) by HS-GC-IMS. The 29 VOCs identified were primarily ketones and aldehydes. Characteristic VOCs responsible for flavor differences were clarified by difference comparison, clustering and PCA analysis. Additionally, variations in lipid and protein were the primary causes of the VOCs differences in EP through microscopy imaging, infrared and fluorescence spectroscopy. EWP's stretched structure favored fishy-smelling VOCs adsorption but limited total aldehyde binding due to strong hydrophobic interaction. EYP's higher ß-sheet ratio and fewer hydrogen bond sites weakened its alcohol VOCs binding capacity. The abundance of ketone VOCs in EP was linked to their low steric hindrance. Therefore, this study elucidated the flavor differences reasons among EWP, EYP and WEP, laying foundation for EP applications in food industry.
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Background Applying topical vancomycin has shown a decrease in the likelihood of surgical site infections (SSIs) in surgeries linked to a heightened risk of severe and resistant infections. Nevertheless, the effectiveness of this prophylactic approach has not been assessed in open ankle surgeries with internal fixation. Objective This study aimed to assess whether topical vancomycin diminishes the risk of SSI in patients with ankle fractures undergoing open reduction with internal fixation. Methods A randomized, controlled, double-blind clinical trial was carried out. Patients were divided into two groups in a 1:1 ratio. The control group received the standard prophylactic treatment with IV cephalothin 1 g, while the intervention group was administered topical vancomycin (1 g) in addition to the standard prophylactic treatment. The main outcomes were the SSI rates at 14 days, 28 days, and three months post-surgery, based on relevant clinical signs and laboratory tests. Results One hundred thirty-two patients were randomized (51.2% female), with 66 subjects included in each intervention arm. A total of 97.7% of them completed the study. Both groups were homogeneous in baseline characteristics. There were two SSIs in both the vancomycin group (3.3%) and the control group (3.5%), with no statistical differences (p = 0.945). The microorganisms isolated as causal agents were Staphylococcus aureus and Acinetobacter baumannii. By the three-month follow-up, no infections were noted in both intervention groups. Conclusion These results indicate that the topical administration of vancomycin may not represent an advantage in preventing SSI in ankle fractures requiring open reduction with internal fixation at the three-month postoperative stage.
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Dry powder inhalers (DPIs) are state-of-the-art pulmonary drug delivery systems. This article explores the transformative impact of nanotechnology on DPIs, emphasizing the Quality Target Product Profile (QTPP) with a focus on aerodynamic performance and particle characteristics. It navigates global regulatory frameworks, underscoring the need for safety and efficacy standards. Additionally, it highlights the emerging field of nanoparticulate dry powder inhalers, showcasing their potential to enhance targeted drug delivery in respiratory medicine. This concise overview is a valuable resource for researchers, physicians, and pharmaceutical developers, providing insights into the development and commercialization of advanced inhalation systems.
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Sistemas de Liberação de Medicamentos , Inaladores de Pó Seco , Inaladores de Pó Seco/métodos , Humanos , Administração por Inalação , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Nanomedicina/métodos , Tamanho da Partícula , Nanotecnologia/métodosRESUMO
Molecular interactions between active pharmaceutical ingredients (APIs) and xanthine (XAT) derivatives were analyzed using singular value decomposition (SVD). XAT derivatives were mixed with equimolar amounts of ibuprofen (IBP) and diclofenac (DCF), and their dissolution behaviors were measured using high-performance liquid chromatography. The solubility of IBP decreased in mixtures with caffeine (CFN) and theophylline (TPH), whereas that of DCF increased in mixtures with CFN and TPH. No significant differences were observed between the mixtures of theobromine (TBR) or XAT with IBP and DCF. Mixtures with various molar ratios were analyzed using differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infrared spectroscopy to further explore these interactions. The results were subjected to SVD. This analysis provides valuable insights into the differences in interaction strength and predicted interaction sites between XAT derivatives and APIs based on the combinations that form mixtures. The results also showed the impact of the XAT derivatives on the dissolution behavior of IBP and DCF. Although IBP and DCF were found to form intermolecular interactions with CFN and TPH, these effects resulted in a reduction of the solubility of IBP and an increase in the solubility of DCF. The current approach has the potential to predict various interactions that may occur in different combinations, thereby contributing to a better understanding of the impact of health supplements on pharmaceuticals.
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The study investigated the effect of Compound Shougong Powder(CSGP) on the biological functions of triple-negative breast cancer(TNBC) cells and whether its mechanism of action was related to the epithelial-mesenchymal transition(EMT) signaling pathway. TNBC cells(MDA-MB-231 and BT-549) were treated with different concentrations of CSGP-containing serum. MTS assay was used to detect the effect of CSGP on the proliferation of TNBC cells. The EdU staining was used to detect the effect of CSGP on the proliferation of TNBC cells. Flow cytometry was used to examine the impact of CSGP on apoptosis of TNBC cells. Wound-healing and Transwell assays were used to evaluate the effects of different concentrations of CSGP on the migration and invasion capabilities of TNBC cells. RNA sequencing technology was utilized to elucidate its mechanism. Subsequently, qRT-PCR was performed to measure the mRNA expression levels of E-cadherin, N-cadherin, Slug, Snail, Vimentin, Twist, Zinc finger E-box-Binding homeobox 1(Zeb1), and Zinc finger E-box-Binding homeobox 2(Zeb2). Western blot was used to assess the protein expression levels of Slug, Vimentin, and E-cadherin. After intervention with CSGP, the proliferation of MDA-MB-231 and BT-549 cells significantly decreased, while the apoptosis rate markedly increased. The expression levels of the epithelial marker protein E-cadherin significantly increased, while the expression levels of the EMT-related transcription factors Slug and Vimentin showed a decrease. In conclusion, CSGP inhibits the EMT, thereby suppressing the malignant progression of TNBC.
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Apoptose , Proliferação de Células , Medicamentos de Ervas Chinesas , Transição Epitelial-Mesenquimal , Neoplasias de Mama Triplo Negativas , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Medicamentos de Ervas Chinesas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Pós/química , Caderinas/genética , Caderinas/metabolismoRESUMO
Active pharmaceutical ingredient (API) embedded dry powder for inhalation (AeDPI) shows higher drug loading and delivery dose for directly treating various lung infections. Inspired by the dandelion, we propose a novel kind of AeDPI microparticle structure fabricated by spray freeze drying technology, which would potentially enhance the alveoli deposition efficiency. When inhaling, such microparticles are expected to be easily broken-up into fragments containing API that acts as 'seed' and could be delivered to alveoli aided by the low density 'pappus' composed of excipient. Herein, itraconazole (ITZ), a first-line drug for treating pulmonary aspergillosis, was selected as model API. TPGS, an amphiphilic surfactant, was used to achieve stable primary ITZ nanocrystal (INc) suspensions for spray freeze drying. A series of microparticles were prepared, and the dandelion-like structure was successfully achieved. The effects of feed liquid compositions and freezing parameters on the microparticle size, morphology, surface energy, crystal properties and in vitro aerosol performance were systematically investigated. The optimal sample (SF(-50)D-INc7Leu3-2) in one-way experiment showed the highest fine particle fraction of â¼ 68.96â¯% and extra fine particle fraction of â¼ 36.87â¯%, equivalently â¼ 4.60â¯mg and â¼ 2.46â¯mg could reach the lung and alveoli, respectively, when inhaling 10â¯mg dry powders. The response surface methodology (RSM) analysis provided the optimized design space for fabricating microparticles with higher deep lung deposition performance. This study demonstrates the advantages of AeDPI microparticle with dandelion-like structure on promoting the delivery efficiency of high-dose drug to the deep lung.
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The physicochemical properties of Nemipterus virgatus surimi gel were investigated, with tremella powder (TP) at concentrations ranging from 0 to 0.5% (w/w) combined with continuous microwave heating (CMH) using water-bath heating (WBH) as control. Results showed that TP addition (0.1%-0.3%, w/w) could significantly enhance the water holding capacity and reduce whiteness and cooking loss, attributed to the changed lateral relaxation time of water distribution. Notably, at 0.3% TP and 80 °C, the gel strength significantly increased by 96.84%, and the hardness, chewiness, and adhesiveness improved, but the quality of surimi decreased above 0.3% TP. The gel network structure was influenced by protein secondary structure composition, especially for increasing ß-sheet in Raman spectra, thus promoting the gel microstructure density and uniform protein distribution. These findings offer insights for enhancing surimi gel quality and broadening tremella application in product processing.
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The current research endeavour aimed to synthesize ferulic acid grafted tamarind gum/guar gum (FA-g-TG/GG) based powders as wound dressings, which could form in situ gels upon contact with wound exudates. In this context, variable amounts of FA were initially grafted with TG via the Steglich esterification reaction protocol and the resulting conjugates were subsequently amalgamated with GG and lyophilized to produce dry powders (F-1 - -F-3) with average particle size within 5.10-5.54 µm and average angle of repose â¼30°. These powders were structurally characterized with 1H NMR, FTIR, DSC, TGA, XRD and SEM analyses. Pristine TG, FA-g-TG and FA-g-TG/GG powders (F-2) revealed their distinct morphological structures and variable negative zeta potential values (-11.06 mV-25.50 mV). Among various formulation (F-1-F-3), F-2 demonstrated an acceptable powder-to-gel conversion time (within 20 min), suitable water vapour transmission rates (WVTR, 2564.94 ± 32.47 g/m2/day) and excellent water retention abilities and swelling profiles (4559.00 ± 41.57 %) in wound fluid. The powders were cytocompatible and conferred antioxidant activities. The powders also displayed fibroblast cell proliferation, migration and adhesion properties, implying their wound-healing potentials. Thus, the developed in situ gel-forming powders could be employed as promising dressings for wound management.