Design and synthesis of novel mitochondria-targeted ergosterol peroxide derivatives as potential anti-cancer agents.

Ergosterol peroxide (EP) is a natural steroid compound that has been reported to have significant antitumor activity. However, its poor water solubility and cellular uptake mean that it has weak efficacy against tumor cells. Herein, we designed and synthesized a series of EP derivatives with mitochondrial targeting properties. Of these, compound 15a showed an IC50 value of 0.32 µM against MCF-7 cells, which was 67-fold higher than that of the parental EP (IC50 = 21.46 µM), and was better than cisplatin (IC50 = 4.23 µM), had a selectivity index of 25.28 (IC50MCF-10A/IC50MCF-7). Additionally, compound 15a promoted an increase in intracellular reactive oxygen species levels and a decrease in mitochondrial membrane potential, and blocked the cell cycle in the G0/G1 phase. In a mouse model of breast cancer, 15a showed 89.85 % tumor inhibition at a dose of 20 mg/kg, which is similar to the therapeutic effect of the cisplatin. On the basis of these results, 15a could be considered for further preclinical evaluation for cancer therapy.

Factors to consider before choosing EV labeling method for fluorescence-based techniques.

A well-designed fluorescence-based analysis of extracellular vesicles (EV) can provide insights into the size, morphology, and biological function of EVs, which can be used in medical applications. Fluorescent nanoparticle tracking analysis with appropriate controls can provide reliable data for size and concentration measurements, while nanoscale flow cytometry is the most appropriate tool for characterizing molecular cargoes. Label selection is a crucial element in all fluorescence methods. The most comprehensive data can be obtained if several labeling approaches for a given marker are used, as they would provide complementary information about EV populations and interactions with the cells. In all EV-related experiments, the influence of lipoproteins and protein corona on the results should be considered. By reviewing and considering all the factors affecting EV labeling methods used in fluorescence-based techniques, we can assert that the data will provide as accurate as possible information about true EV biology and offer precise, clinically applicable information for future EV-based diagnostic or therapeutic applications.

A Meta-Analysis of Randomized Controlled Trials Comparing the Efficacy and Safety of Hydrophilic Versus Lipophilic Statins in Acute Coronary Syndrome Patients.

Statins differ in their solubility. Some previous studies suggested a difference in clinical efficacy and adverse events between hydrophilic and lipophilic statins. The purpose of this study is to compare the efficacy and safety of hydrophilic and lipophilic statins in patients with acute coronary syndrome. The databases of MEDLINE/PubMed, Cochrane Library, the Web of Science, and Scopus were systemically searched for articles published from inception until the 18th of July 2024. The primary outcome included major adverse cardiac events (MACE), while the secondary outcomes included myocardial infarction (MI), unstable angina (UA), revascularization, stroke, all-cause mortality, cardiovascular deaths, and adverse events. The results were pooled as risk ratio (RR) along with their 95% confidence intervals (CI). Nine studies were included. Hydrophilic statins showed a significantly higher risk of MACE and UA compared to lipophilic statins (RR 1.11 [95% CI 1.02, 1.21] and 1.30 [95% CI 1.04, 1.62]), but subgroup analysis showed a lack of significant difference between statins of similar intensity (1.01 [95% CI 0.86, 1.18] and 0.98 [0.67, 1.45], respectively). Both statins showed comparable results regarding the occurrence of MI (1.18 [95% CI 0.98, 1.40]), revascularization (1.09 [95% CI 0.99, 1.20]), stroke (1.16 [95% CI 0.80, 1.66]), all-cause mortality (1.13 [95% CI 0.92, 1.38]), cardiovascular deaths (1.14 [95% CI 0.76, 1.72]), adverse events leading to discontinuation (1.03 [95% CI 0.56, 1.90]), increased alanine aminotransferase (0.61 [95% CI 0.32, 1.16]), increased creatine kinase (0.90 [95% CI 0.30, 2.72]), and increased serum creatinine (1.03 [95% CI 0.49, 2.19]). The efficacy and safety of hydrophilic and lipophilic statins are comparable when the cholesterol-lowering intensity of statins is similar. This suggests that intensity, rather than the lipophilicity of the statin, plays a more important role in the secondary prevention of MACE and individual adverse events.

Water-Soluble Lipophilic Near-Infrared Region II Fluorophores for High-Brightness Lipid Layer and Lipid Droplets Imaging Applications.

Fluorescence imaging in the second near-infrared region (NIR-II, 1000-1700 nm) has garnered considerable attention for displaying the biological information of deep tissues. However, the lack of biocompatible contrast agents with bright NIR-II emission has hampered the precise clinical application of deep tissue imaging. Here, a lipophilic enhancement strategy employing donor-acceptor-donor (D-A-D) molecules, introducing long alkoxy chains and quaternary ammonium salts for the development of highly bright water-soluble NIR-II fluorophores (BBTD-2C-N), is described. Notably, liposome-encapsulated BBTD-2C-N nanoparticles (B-2C-N/DMPC) in aqueous solution exhibit a 1.8-fold increase in NIR-II fluorescence brightness compared to free BBTD-2C-N in methanol. Avoidance of the aggregation-caused quenching effect and enhanced NIR-II fluorescence are attributed to significantly attenuated π-π stacking interactions and maintained monodisperses in the hydrophobic liposome shell. Moreover, BBTD-2C-N demonstrates superior performance in visualizing lipid droplet-rich HeLa cells in vitro, as well as precise monitoring of adipose tissue and fatty liver in vivo. This study reveals a new avenue for the development of bright NIR-II fluorophores and precise in vivo imaging.

Design, synthesis and antitumor effects of lupeol quaternary phosphonium salt derivatives.

Lupeol is a natural pentacyclic triterpenoid with a wide range of biological activities. To improve the water solubility and targeting of lupeol, in the following study, we synthesized 27 lupeol derivatives in the first series by introducing lipophilic cations with lupeol as the lead compound. Through the screening of different cancer cells, we found that some of the derivatives showed better activity than cisplatin against human non-small cell lung cancer A549 cells, among which compound 6c was found to have an IC50 value of 1.83 µM and a selectivity index of 21.02 (IC50MRC-5/IC50A549) against A549 cells. To further improve the antiproliferative activity of the compounds, we replaced the ester linkage of the linker with a carbamate linkage and synthesized a second series of five lupeol derivatives which were screened for activity, among which compound 14f was found to have an IC50 value of 1.36 µM and a selectivity index of 15.60 (IC50MRC-5/IC50A549) against A549 cells. We further evaluated the bioactivity of compounds 6c and 14f and found that both compounds induced apoptosis in A549 cells, promoted an increase in intracellular reactive oxygen species and decrease in mitochondrial membrane potential, and inhibited the cell cycle in the S phase. Of the compounds, compound 14f showed stronger bioactivity than compound 6c. We then selected compound 14f for molecular-level Western blot evaluation and in vivo evaluation in the zebrafish xenograft A549 tumor cell model. Compound 14f was found to significantly downregulate Bcl-2 protein expression and upregulate Bax, Cyt C, cleaved caspase-9, and cleaved caspase-3 protein expression, and 14f was found to be able to inhibit the proliferation of A549 cells in the zebrafish xenograft model. The above results suggest that compound 14f has great potential in the development of antitumor drugs targeting mitochondria.

Lipophilic derivatives of EGCG as potent α-amylase and α-glucosidase inhibitors ameliorating oxidative stress and inflammation.

Uncontrolled hyperglycemia leads to increased oxidative stress, chronic inflammation, and insulin resistance, rendering diabetes management harder to accomplish. To tackle these myriads of challenges, researchers strive to explore innovative multifaceted treatment strategies, including inhibiting carbohydrate hydrolases. Herein, we report alkyl-ether EGCG derivatives as potent α-amylase and α-glucosidase inhibitors that could simultaneously ameliorate oxidative stress and inflammation. 4″-C18 EGCG, the most promising compound, showed multifold improvement in glycaemic management compared to acarbose, with 230-fold greater inhibition (competitive) of α-glucosidase (IC50 0.81 µM) and 3-fold better inhibition of α-amylase (IC50 3.74 µM). All derivatives showed stronger antioxidant activity (IC50 6.16-15.76 µM) than vitamin C, while acarbose showed none. 4″-C18 EGCG also downregulated pro-inflammatory cytokines and showed no significant cytotoxicity up to 50 µM in primary human peripheral blood mononuclear cells (PBMC), non-cancerous cell line, 3T3-L1 and HEK 293. The in silico binding affinity analysis of 4″-C18 EGCG with α-amylase and α-glucosidase was found to exhibit a good extent of interaction as compared to acarbose. In comparison to EGCG, 4″-Cn EGCG derivatives were found to remain stable in the physiological conditions even after 24 h. Together, the reported molecules demonstrated multifaceted antidiabetic potential inhibiting carbohydrate hydrolases, reducing oxidative stress, and inflammation, which are known to aggravate diabetes.

Development of a hydrophilic-lipophilic-balanced copolymer@zirconium-based metal-organic framework-based solid-phase microextraction probe for the trace determination of organophosphorus pesticides in tea infusions.

Organophosphorus pesticides (OPPs) present in tea infusions pose a serious threat to human health. In this study, a sensitive method for the determination of OPPs was developed based on a direct-immersion solid-phase microextraction (DI-SPME) probe. By fine adjustment of the ratio and one-step polymerization of dihydroxy-functionalized zirconium-based metal-organic framework UiO-66-(OH)2 and divinylbenzene-N-vinyl pyrrolidone (DVB-NVP) microspheres, the DVB-NVP@ UiO-66-(OH)2 (D-N@U) composite with an optimal hydrophilic-lipophilic balance (HLB) was achieved. Furthermore, D-N@U was adhesively bonded to stainless-steel wires to fabricate a DI-SPME probe. OPPs, especially those with nonpolar properties characterized by a high octanol-water partition coefficient (log KOW), were selectively and efficiently enriched on the D-N@U-coated DI-SPME probe from tea infusions. Coupled with a gas chromatography-flame photometric detector, the as-fabricated D-N@U-coated DI-SPME probe achieved good performance for OPPs analysis with a wide linear dynamic range of 0.10-500.00 µg/L and low detection limits of 1.96-6.69 ng/L. Moreover, in spiked samples, the recoveries and relative standard deviations were in the ranges of 73.12%-101.20 % and 1.03%-6.56 %, respectively. Owing to its simple operation, high extraction efficiency, and high sensitivity, this approach has great potential for the rapid determination of multiple pesticide trace-level residues in food.

Development of Mixed Micelles for Enhancing Fenretinide Apparent Solubility and Anticancer Activity Against Neuroblastoma Cells.

INTRODUCTION/OBJECTIVES: The purpose of the study was to evaluate the suitability of mixed micelles prepared with D-α-tocopheryl polyethylene glycol succinate (TPGS) and 1,2- distearoyl-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) to encapsulate the poorly soluble anticancer drug fenretinide (4-HPR). METHODS: After assaying the solubilization ability of the surfactants by the equilibrium method, the micelles were prepared using the solvent casting technique starting from different 4-HPR:TPGS: DSPE-PEG w/w ratios. The resulting formulations were investigated for their stability under storage conditions and upon dilution, modelling the reaching of physiological concentrations after intravenous administration. The characterization of micelles included the determination of DL%, EE %, particle size distribution, Z-potential, and thermal analysis by DSC. The cytotoxicity studies were performed on HTLA-230 and SK-N-BE-2C neuroblastoma cells by the MTT essay. RESULTS: The colloidal dispersions showed a mean diameter of 12 nm, negative Zeta potential, and a narrow dimensional distribution. 4-HPR was formulated in the mixed micelles with an encapsulation efficiency of 88% and with an increment of the apparent solubility of 363-fold. The 4-HPR entrapment remained stable up to the surfactants' concentration of 2.97E-05 M. The loaded micelles exhibited a slow-release behaviour, with about 28% of the drug released after 24 h. On the most resistant SK-N-BE-2C cells, the encapsulated 4-HPR was significantly more active than free 4-HPR in reducing cell viability. CONCLUSION: Loaded micelles demonstrated their suitability as a new adjuvant tool potentially useful for the treatment of neuroblastoma.

Potentiometry in determining the antioxidant capacity of compounds of different hydrophilicity in the joint presence using mixed solvents and surfactants.

In this work, for the first time, the potentiometric method was used to determine the antioxidant capacity (AOC) of compounds of different hydrophilicity in the joint presence using mixed solvents and surfactants. The AOC of model solutions of antioxidants of different hydrophilicity was determined separately and in the joint presence in the media of phosphate buffer-surfactant and mixed solvents-surfactant, using as an example the ascorbic acid and the α-tocopherol. It was shown that the surfactant Triton X-100 is able to solubilize α-tocopherol under the selected conditions, allows to obtain reproducible and accurate results, and has less effect on the equilibrium rate of the K3[Fe(CN)6]/K4[Fe(CN)6] system. Phosphate buffer-ethanol and phosphate buffer-acetonitrile media in the 3:2 ratio with Triton X-100 (5 mmol/dm3) were chosen as the analysis conditions (RSD ≤ 6%). The range of determined concentrations was (0.006-0.5) m mmol/dm3 in phosphate buffer-ethanol and (0.006-0.3) m mmol/dm3 in phosphate buffer-acetonitrile. AOC of raw materials infusions was determined in selected media. The positive correlation with the well-known Folin-Ciocalteu assay was obtained.

Development of amphiphilic hypercrosslinked porous polymers for magnetic extraction of multiple environmental pollutants in water.

Under the principle of similar compatibility, researchers have developed various polarity extractants corresponding to a class of chemicals. Separating different polarities chemicals with one extractant effectively has become a novel research trend in separation science. Given the complexity of environmental sample matrices and the significant differences in polarity and solubility of various compounds, the introduction of hydrophilic groups to hydrophobic material skeletons can lead to sorbents with hydrophilic-lipophilic balance (HLB) property and thus improve their extraction performance for substances with different polarities. In this work, a hypercrosslinked polymer (HCPPz-TPB), designated as HLB, was synthesized by incorporating polar pyrazine and nonpolar triphenylbenzene molecules within each other. Subsequently, a core-shell magnetic composite material was obtained by encapsulating magnetic Fe3O4 nanoparticles in HCPPz-TPB. The material was applied as an adsorbent for magnetic solid phase extraction (MSPE) and combined with a high-performance liquid chromatography-photodiode array detector (HPLC-PDA) to enrich, separate, and detect seven polar contaminants in environmental water samples. The proposed approach, Fe3O4@SiO2@HCPPz-TPB-MSPE-HPLC-PDA, is characterized by its outstanding high sensitivity, low detection limits, wide linear range, and good reproducibility. The method demonstrated satisfactory linearity in the range of 0.05-2 µg mL-1 with R2 values between 0.9969 and 0.9997; the limits of detection (LOD) were observed to be within the range of 0.0019-0.016 µg L-1, and limits of quantification (LOQ) was observed to be within the range of 0.0064-0.054 µg L-1 range with good precision. The recoveries of the different contaminants in the environmental samples ranged from 83.61 to 116.46% (RSD≤10.56, n = 5). The new hydrophilic-lipophilic balance extractant is highly efficient, sensitive, and precise for extracting different polar pollutants. The findings demonstrate that the Fe3O4@SiO2@HCPPz-TPB display a remarkable affinity for multiple targets, driven by complex interactions including multi-stackings and hydrogen bonding as a sorbent. The synthesized Fe3O4@SiO2@HCPPz-TPB may be employed in diverse applications, including extraction, removal, and determination of diverse trace multi-target analytes in complex media.

Developing Self-Nanoemulsifying Drug Delivery Systems Comprising an Artemether-Lumefantrine Fixed-Dose Combination to Treat Malaria.

BACKGROUND: Despite attempts to control malaria, poor drug bioavailability means malaria still places enormous pressure on health globally. It has been found that the solubility of highly lipophilic compounds can be enhanced through lipid formulations, e.g., self-emulsifying drug delivery systems (SEDDSs). Thus, quality-by-design and characterization were used to justify the development and determine the feasibility of oral oil-in-water SEDDSs comprising a fixed-dose combination (FDC) of artemether-lumefantrine to treat malaria more effectively without the aid of a fatty meal. These formulations were compared to a commercial product containing the same active compounds. METHODS: Excipient compatibility and spontaneous emulsification capacity of different FDC-excipient combinations were identified by employing isothermal microcalorimetry, solubility, and water titration tests. Pseudoternary phase diagrams were constructed, and checkpoint formulations were selected within the self-emulsification region by reviewing formulation properties essential for optimized drug delivery. SEDDSs capable of enduring phase separation within 24 h were subjected to characterization experiments, i.e., drug concentration determination, cloud point, droplet size, size distribution, self-emulsification time, self-emulsification efficacy, viscosity, zeta potential, and thermodynamic stability analysis. SEDDSs with favorable characteristics were identified in the micro or nano range (SNEDDSs) before being subjected to drug release studies. RESULTS: All final formulations depicted enhanced artemether and lumefantrine release compared to the commercial product, which could not release lumefantrine at a quantifiable concentration in this study. The avocado oil (AVO)4:6 and olive oil (OLV)3:7 SNEDDSs overall portrayed the ideal characteristics and depicted the highest percentage of drug release. CONCLUSIONS: This study offers evidence that SNEDDSs from selected natural oils comprising an artemether-lumefantrine FDC can potentially enhance the bioavailability of these lipophilic drugs.

Fabrication of Poly Lactic-co-Glycolic Acid Microneedles for Sustained Delivery of Lipophilic Peptide-Carfilzomib.

Transdermal drug delivery (TDD) is an attractive route of administration, providing several advantages, especially over oral and parenteral routes. However, TDD is significantly restricted due to the barrier imposed by the uppermost layer of the skin, the stratum corneum (SC). Microneedles is a physical enhancement technique that efficiently pierces the SC and facilitates the delivery of both lipophilic and hydrophilic molecules. Dissolving microneedles is a commonly used type that is fabricated utilizing various biodegradable and biocompatible polymers, such as polylactic acid, polyglycolic acid, or poly(lactide-co-glycolide) (PLGA). Such polymers also promote the prolonged release of the drug due to the slow degradation of the polymer matrix following its insertion. We selected carfilzomib, a small therapeutic peptide (MW: 719.924 g/mol, log P 4.19), as a model drug to fabricate a microneedle-based sustained delivery system. This study is a proof-of-concept investigation in which we fabricated PLGA microneedles using four types of PLGA (50-2A, 50-5A, 75-5A, and 50-7P) to evaluate the feasibility of long-acting transdermal delivery of carfilzomib. Micromolding technique was used to fabricate the PLGA microneedles and characterization tests, including Fourier transform infrared spectroscopy, insertion capability using the skin simulant Parafilm model, histological evaluation, scanning electron microscopy, and confocal microscopy were conducted. In vitro release and permeation testing were conducted in vertical Franz diffusion cells. N-methyl pyrrolidone was utilized as the organic solvent and microneedles were solidified in controlled conditions, which led to good mechanical strength. Both in vitro release and permeation testing showed sustained profiles of carfilzomib over 7 days. The release and permeation were significantly influenced by the molecular weight of PLGA and the lipophilic properties of carfilzomib.

Lyotropic liquid crystal emulsions of LAVR-289: Influence of internal mesophase structure on cytotoxicity and in-vitro antiviral activity.

Emerging and reemerging viruses pose significant public health threats, underscoring the urgent need for new antiviral drugs. Recently, a novel family of antiviral acyclic nucleoside phosphonates (ANP) composed of a 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl phosphonic acid skeleton (O-DAPy nucleobase) has shown promise. Among these, LAVR-289 stands out for its potent inhibitory effects against various DNA viruses. Despite its efficacy, LAVR-289s poor water solubility hampers effective drug delivery. To address this, innovative delivery systems utilizing lipidic derivatives have been explored for various administration routes. Submicron lyotropic liquid crystals (LLCs) are particularly promising drug carriers for the encapsulation, protection, and delivery of lipophilic drugs like LAVR-289. This study focuses on developing submicron-sized lipid mesophase dispersions, including emulsified L2 phase, cubosomes, and hexosomes, by adjusting lipidic compounds such as Dimodan® U/J, Lecithins E80, and Miglyol® 812 N. These formulations aim to enhance the solubility and bioavailability of LAVR-289. In vitro evaluations demonstrated that LAVR-289-loaded LLCs at a concentration of 1 µM efficiently inhibited vaccinia virus in infected human cells, with no observed cytotoxicity. Notably, hexosomes exhibited the most favorable antiviral outcomes, suggesting that the internal mesophase structure plays a critical role in optimizing the therapeutic efficacy of this drug class.

On-site extraction of benzophenones from swimming pool water using hybrid tapes based on the integration of hydrophilic-lipophilic balance microparticles and an outer magnetic nanometric domain.

An on-site extraction device is presented consisting of scotch tape modified with concentric domains of micrometric hydrophilic-lipophilic balance (HLB) particles surrounded by a ring of nanometric magnetic ones. On the one hand, HLB microparticles are readily available at the surface of the tape, exposed to interact with the target analytes, being responsible for the extraction capacity of the sorptive phase. On the other hand, the presence of magnetic nanoparticles enables the attachment of the modified tape onto a metallic screw via a magnet, which is then coupled to a wireless drill, enabling the stirring of the microextraction device. Both are simply fixed to the cost-effective, flexible, and versatile support, i.e., scotch tape, owing to their adhesive properties. The microextraction device has been applied to the determination of six benzophenones in swimming pool water samples. The variables that may affect the extraction process have been evaluated. Under the optimum conditions and using liquid chromatography-tandem mass spectrometry as the instrumental technique, the method provided a limit of detection of 0.03 µg L-1. The intra-day precision, evaluated at three different concentration levels and expressed as relative standard deviation, was lower than 10%, which also comprises the variability within single-use sorptive tapes. The accuracy, calculated with spiked samples and expressed as relative recovery, ranged from 71 to 138%. The method was applied to the analysis of swimming pool water, revealing the presence of such compounds.

Synthesis of lipophilic vitamin C and evaluation of its antioxidant performance in sunflower seed oil frying.

The present study involved the synthesis and analysis of a lipophilic form of vitamin C, namely tetrabutyryl vitamin C ester (TVCE). TVCE is synthesized by a simple one-step method, combining the advantages of VC and butyric acid. Its antioxidant efficacy on sunflower seed oil frying was evaluated by assessing lipid oxidation parameters including peroxide number (POV), carbonyl number (CV), and paraniline number (pAV). Furthermore, changes in the fatty acid composition of the oil were monitored using techniques such as infrared spectroscopy (IR), nuclear magnetic resonance (NMR), and gas chromatography (GC). The findings demonstrated that lipophilic vitamin C exhibited superior protection against oxidation during frying compared to vitamin E, suggesting that it may be an effective fat-soluble antioxidant. The study provides a new field for the utilization of vitamin C and a new idea for the development of efficient antioxidants.

Reversed phase HPLC with UHPLC benefits for the determination of tocochromanols in the seeds of edible fruits in the Rosaceae family.

Rosaceae family includes several edible fruit species processed in vast quantities and generates large amounts of seeds valuable in tocopherols. In the present study, the composition of tocochromanols in the seeds of 141 samples was determined by reversed phase high-performance liquid chromatography (RPLC) with diode array detector (DAD), fluorescence detector (FLD) and confirmed by mass detector (MS). The thirteen species belonging to the Rosaceae family were classified by multivariate statistical analysis, hierarchical cluster analysis (HCA) and principal component analysis (PCA) into two groups based on tocochromanols content. Group 'A' includes pears (Pyrus communis), sweet cherry (Prunus avium), sour cherry (Prunus cerasus), apricots (Prunus armeniaca), hexaploid plums (Prunus domestica), diploid plums (Prunus cerasifera), raspberry (Rubus idaeus), and rose hip (Rosa rugosa); while group 'B' quince (Cydonia oblonga), Japanese quince (Chaenomeles japonica), strawberry (Fragaria × ananassa), dessert apples (Malus domestica), and crab apples (Malus spp.). Two rapid (6-7 min) and low pressure (7.2-8.1 MPa) separation methods were developed and validated using two core-shell columns (i) C18 and (ii) F5. The F5 achieved a separation of ß and γ isomers while the C18 column did not.

The Association between Statin Use and Reduced Migraine Likelihood: A Comprehensive Analysis of Migraine Subtypes and Statin Types in a Nationwide Korean Cohort.

Despite growing interest in the preventive effects of statins, as lipid-lowering agents, on migraine attacks, comprehensive nationwide studies comparing migraine likelihood between statin users and controls are lacking. Our nested case-control study within the Korean National Health Insurance Service-Health Screening Cohort (2002-2019) investigated this association using 38,957 migraine patients and 155,828 controls, considering migraine subtypes (with/without aura) and statin types (lipophilic vs. hydrophilic). Using propensity score matching and adjusting for confounders, statin use was linked to reduced migraine likelihood overall (odds ratio (OR) 0.93), particularly for migraines with aura (OR 0.75) and without aura (OR 0.94). Lipophilic statins were effective for both subtypes, while hydrophilic statins mainly reduced the likelihood of migraines without aura. Subgroup analyses showed consistent benefits across demographics, but varied effectiveness based on weight, smoking, alcohol use, hemoglobin levels, and dyslipidemia history. In summary, this nationwide cohort study suggests that statin use may reduce migraine likelihood among Korean adults across diverse demographics and clinical profiles, but varied effectiveness based on certain lifestyle and comorbidity factors underscores the importance of considering individual patient profiles when assessing the potential benefits of statin therapy for migraine prevention.

Co-encapsulation of vitamin E and quercetin by soybean lipophilic proteins based on pH-shifting and ultrasonication: Focus on interaction mechanisms, structural and physicochemical properties.

This study explored the mechanism of interaction of pH-shifting combined ultrasonication and its effect on soybean lipophilic proteins (SLP) and the potential of modified SLP as the carrier for vitamin E (VE) and quercetin (QU). The spectroscopy results revealed that both VE and QU changed the SLP conformation and exposed hydrophobic groups. The loading rates of VE and QU by SLP with alkaline pH-shifting combined with ultrasonication (300 w,20 min) were 86.91% and 75.99%, respectively. According to the antioxidant analysis, with an increase in the ultrasonication power, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging capacity of the samples increased, where the DPPH and ABTS radical scavenging capacity of sample SQV-6 were 70.90% and 63.43%, respectively. The physicochemical properties, microstructure, and stability of the SLP-VE-QU complex improved significantly. Overall, the present findings broadened the application of simple structural carriers for co-encapsulating functional factors.

Analysis of lipophilic fingerprints of edible wild rhubarb (Rheum ribes L.) using GC-MS combined with chemometrics.

Rhubarb (Rheum ribes L.) is used globally as both a food supplement and a vegetable. The lipophilic fingerprints of wild rhubarb of Turkiye origin were investigated by gas chromatography-mass spectrometry (GC-MS) combined with chemometrics, including hierarchical cluster analysis (HCA) and principal component analysis (PCA). GC-MS results identified a total of 72 lipophi6lic compounds, including fatty acids, fatty acid esters, simple hydrocarbons and other organics, in all parts of the plant. PCA and HCA analyses revealed intraspecific lipophilic component variation among six wild rhubarb populations, as well as significant variation among lipophilic fingerprints in leaves, fruits, flowers, and roots. Among the compounds, palmitic acid, α-linolenic acid, ethyl palmitate, ethyl oleate, linoleic acid ethyl ester and n-tetracosane were important for the overall lipophilic fingerprints of all parts of the rhubarb. These findings highlight the potential of using HCA and PCA analysis in combination with GC-MS fingerprints as an effective analytical approach.

Vaginal Ovule Loaded with Bismuth Lipophilic Nanoparticles and Cetylpyridinium Chloride Inhibits Human Cervical Carcinoma and Candida albicans Growth.

Bismuth lipophilic nanoparticles (BisBAL NPs) and cetylpyridinium chloride (CPC) are antineoplastic and antimicrobial in vitro. As a next pre-clinical step, a clinically viable dosage form for vaginal application was developed. Compendial pharmacopeial tests (mass uniformity, disintegration, and compressive mechanics) and inductively coupled plasma optical emission spectroscopy were conducted on in-house developed glycerinated gelatin (60:15 v/w) vaginal ovules containing BisBAL NP-CPC. The antimycotic activity of BisBAL NP-CPC vaginal ovules was analyzed using disk diffusion and cell viability XTT assays. The antitumor properties of BisBAL NP-CPC vaginal ovules were assessed by cell viability MTT tests. BisBAL NP-CPC and drug-free vaginal ovules deposited into ex vivo porcine vaginas disaggregated without signs of adverse cytotoxicity within the timespan of clinical efficacy. BisBAL NP-CPC vaginal ovules demonstrated antifungal efficacy comparable to miconazole: C. albicans growth inhibition haloes in diffusion tests were 23 ± 0.968 mm (n = 3) for BisBAL NP-CPC and 20.35 ± 0.899 mm (n = 3) for miconazole. Likewise, BisBAL NP-CPC vaginal ovules reduced HeLa cell growth by 81%, outperforming the clinical reference of 500 µM 5-fluouracil, which induced a 70% growth inhibition. BisBAL NP-CPC incorporated into glycerinated gelatin vaginal ovules constitute an innovative drug delivery system for topical antimycotic and anti-cervical carcinoma treatments.