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Molecules (Basel, Switzerland) May 2024Fullerene-based amphiphiles are new types of monomers that form self-assemblies with profound applications. The conical fullerene amphiphiles (CFAs) have attracted...
Fullerene-based amphiphiles are new types of monomers that form self-assemblies with profound applications. The conical fullerene amphiphiles (CFAs) have attracted attention for their uniquely self-assembled structures and have opened up a new field for amphiphile research. The CFAs and CFAs with different substances embedded in cavities are designed and their self-assembly behaviors are investigated using molecular dynamics (MD) simulations. The surface and internal structures of the micelles are analyzed from various perspectives, including micelle size, shape, and solvent-accessible surface area (SASA). The systems studied are all oblate micelles. In comparison, embedding Cl or embedding Na in the cavities results in larger micelles and a larger deviation from the spherical shape. Two typical configurations of fullerene surfactant micelles, quadrilateral plane and tetrahedral structure, are presented. The dipole moments of the fullerene molecules are also calculated, and the results show that the embedded negatively charged Cl leads to a decrease in the polarity of the pure fullerene molecules, while the embedded positively charged Na leads to an increase.
PubMed: 38792216
DOI: 10.3390/molecules29102355 -
Molecules (Basel, Switzerland) May 2024The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment... (Review)
Review
The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment pathologies. Emerging as a promising solution to these challenges, nanotechnology-based platforms-including but not limited to liposomes, dendrimers, and micelles-have shown the potential to revolutionize ophthalmic therapeutics. These nanocarriers enhance drug bioavailability, increase residence time in targeted ocular tissues, and offer precise, localized delivery, minimizing systemic side effects. Focusing on pediatric ophthalmology, particularly on retinoblastoma, this review delves into the recent advancements in functionalized nanosystems for drug delivery. Covering the literature from 2017 to 2023, it comprehensively examines these nanocarriers' potential impact on transforming the treatment landscape for retinoblastoma. The review highlights the critical role of these platforms in overcoming the unique pediatric eye barriers, thus enhancing treatment efficacy. It underscores the necessity for ongoing research to realize the full clinical potential of these innovative drug delivery systems in pediatric ophthalmology.
Topics: Retinoblastoma; Humans; Drug Delivery Systems; Drug Carriers; Child; Nanoparticles; Micelles; Liposomes; Dendrimers; Retinal Neoplasms; Administration, Ophthalmic; Nanotechnology
PubMed: 38792122
DOI: 10.3390/molecules29102263 -
International Journal of Molecular... May 2024Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and... (Review)
Review
Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and environmental triggers. Application of emollients and topical drugs such as corticosteroids and calcineurin inhibitors form the mainstay of treatments for this challenging condition. This review aims to summarize the recent advances made in phytochemical-based topical applications to treat AD and the different carriers that are being used. In this review, the clinical efficacy of several plant extracts and bioactive phytochemical compounds in treating AD are discussed. The anti-atopic effects of the herbs are evident through improvements in the Scoring Atopic Dermatitis (SCORAD) index, reduced epidermal thickness, decreased transepidermal water loss, and alleviated itching and dryness in individuals affected by AD as well as in AD mouse models. Histopathological studies and serum analyses conducted in AD mouse models demonstrated a reduction in key inflammatory factors, including thymic stromal lymphopoietin (TSLP), serum immunoglobulin E (IgE), and interleukins (IL). Additionally, there was an observed upregulation of the filaggrin (FLG) gene, which regulates the proteins constituting the stratum corneum, the outermost layer of the epidermis. Carriers play a crucial role in topical drug applications, influencing dose delivery, retention, and bioavailability. This discussion delves into the efficacy of various nanocarriers, including liposomes, ethosomes, nanoemulsions, micelles, nanocrystals, solid-lipid nanoparticles, and polymeric nanoparticles. Consequently, the potential long-term side effects such as atrophy, eruptions, lymphoma, pain, and allergic reactions that are associated with current topical treatments, including emollients, topical corticosteroids, topical calcineurin inhibitors, and crisaborole, can potentially be mitigated through the use of phytochemical-based natural topical treatments.
Topics: Humans; Filaggrin Proteins; Animals; Phytochemicals; Eczema; Plant Extracts; Administration, Topical; Dermatitis, Atopic
PubMed: 38791412
DOI: 10.3390/ijms25105375 -
Foods (Basel, Switzerland) May 2024The effect of shear on heat-induced changes in milk protein concentrate suspensions was examined at different pH levels, revealing novel insights into micellar...
The effect of shear on heat-induced changes in milk protein concentrate suspensions was examined at different pH levels, revealing novel insights into micellar dissociation and protein aggregation dynamics. Milk protein concentrate suspensions, adjusted to pH of 6.1, 6.4, 6.8, or 7.5, underwent combined heat (90 °C for 5 min or 121 °C for 2.6 min) and shear (0, 100, or 1000 s) treatment. The fragmentation of protein aggregates induced by shear was evident in the control MPC suspensions at pH 6.8, irrespective of the temperature. At pH 7.5, shear increased the heat-induced micellar dissociation. This effect was particularly pronounced at 121 °C and 1000 s, resulting in reduced particle size and an elevated concentration of κ-casein (κ-CN) in the non-sedimentable phase. At pH 6.1 or 6.4, shear effects were dependent on sample pH, thereby modifying electrostatic interactions and the extent of whey protein association with the micelles. At pH 6.1, shear promoted heat-induced aggregation, evidenced by an increase in particle size and a significant decline in both whey proteins and caseins in the non-sedimentable phase. At pH 6.4, shear-induced fragmentation of aggregates was observed, prominently due to comparatively higher electrostatic repulsions and fewer protein interactions. The influence of shear on heat-induced changes was considerably impacted by initial pH.
PubMed: 38790816
DOI: 10.3390/foods13101517 -
Journal of the American Chemical Society Jun 2024High-resolution structural NMR analyses of membrane proteins are challenging due to their large size, resulting in broad resonances and strong signal overlap. Among the...
High-resolution structural NMR analyses of membrane proteins are challenging due to their large size, resulting in broad resonances and strong signal overlap. Among the isotope labeling methods that can remedy this situation, segmental isotope labeling is a suitable strategy to simplify NMR spectra and retain high-resolution structural information. However, protein ligation within integral membrane proteins is complicated since the hydrophobic protein fragments are insoluble, and the removal of ligation side-products is elaborate. Here, we show that a stabilized split-intein system can be used for rapid and high-yield protein trans-splicing of integral membrane proteins under denaturing conditions. This setup enables segmental isotope labeling experiments within folded protein domains for NMR studies. We show that high-quality NMR spectra of markedly reduced complexity can be obtained in detergent micelles and lipid nanodiscs. Of note, the nanodisc insertion step specifically selects for the ligated and correctly folded membrane protein and simultaneously removes ligation byproducts. Using this tailored workflow, we show that high-resolution NMR structure determination is strongly facilitated with just two segmentally isotope-labeled membrane protein samples. The presented method will be broadly applicable to structural and dynamical investigations of (membrane-) proteins and their complexes by solution and solid-state NMR but also other structural methods where segmental labeling is beneficial.
Topics: Membrane Proteins; Isotope Labeling; Nuclear Magnetic Resonance, Biomolecular
PubMed: 38787792
DOI: 10.1021/jacs.4c03294 -
Antibiotics (Basel, Switzerland) May 2024Ticks transmit a variety of pathogens to their hosts by feeding on blood. The interactions and struggle between tick pathogens and hosts have evolved bilaterally. The...
Ticks transmit a variety of pathogens to their hosts by feeding on blood. The interactions and struggle between tick pathogens and hosts have evolved bilaterally. The components of tick saliva can directly or indirectly trigger host biological responses in a manner that promotes pathogen transmission; however, host cells continuously develop strategies to combat pathogen infection and transmission. Moreover, it is still unknown how host cells develop their defense strategies against tick-borne viruses during tick sucking. Here, we found that the tick saliva peptide HIDfsin2 enhanced the antiviral innate immunity of mouse macrophages by activating the Toll-like receptor 4 (TLR4) signaling pathway, thereby restricting tick-borne severe fever with thrombocytopenia syndrome virus (SFTSV) replication. HIDfsin2 was identified to interact with lipopolysaccharide (LPS), a ligand of TLR4, and then depolymerize LPS micelles into smaller particles, effectively enhancing the activation of the nuclear factor kappa-B (NF-κB) and type I interferon (IFN-I) signaling pathways, which are downstream of TLR4. Expectedly, TLR4 knockout completely eliminated the promotion effect of HIDfsin2 on NF-κB and type I interferon activation. Moreover, HIDfsin2 enhanced SFTSV replication in TLR4-knockout mouse macrophages, which is consistent with our recent report that HIDfsin2 hijacked p38 mitogen-activated protein kinase (MAPK) to promote the replication of tick-borne SFTSV in A549 and Huh7 cells (human cell lines) with low expression of TLR4. Together, these results provide new insights into the innate immune mechanism of host cells following tick bites. Our study also shows a rare molecular event relating to the mutual antagonism between tick-borne SFTSV and host cells mediated by the tick saliva peptide HIDfsin2 at the tick-host-virus interface.
PubMed: 38786177
DOI: 10.3390/antibiotics13050449 -
BMC Complementary Medicine and Therapies May 2024This study investigated the effect of curcumin nanomicelle (CUR-n) on the structure of testis tissue, the process of spermatogenesis, LH, FSH, testosterone, and...
BACKGROUND
This study investigated the effect of curcumin nanomicelle (CUR-n) on the structure of testis tissue, the process of spermatogenesis, LH, FSH, testosterone, and oxidative stress in a model of multiple sclerosis.
METHODS
Twenty-four male mice C57BL/6 were randomly allocated into 4 groups of 6 (1: group receiving 2% CPZ diet, 2: group receiving the diet of 2% CPZ + CUR-n with a dose of 50 mg/kg, 3: group receiving the diet of 2% CPZ + CUR-n with a dose of 100 mg/kg). The concentration of hormones (testosterone, LH and FSH), was measured by the special hormone assay ELISA kits. Measuring total antioxidant capacity (TAC) and Malondialdehyde (MDA) levels was done by spectrophotometry and calorimetric methods, respectively. Stereological analysis was done in order to explore the number of spermatogenesis cells, testis and sperm properties.
RESULTS
The results indicated that CUR-n (100 mg/kg) significantly enhanced the concentration of LH, FSH, testosterone, and TAC but reduced MDA levels. It also notably increased the quantity of spermatogonia, spermatocyte, round spermatids, long spermatids and LCs, augmented testis weight and volume, and germinal epithelium volume, improved sperm count, morphology, viability, and motility. In addition, a considerable decrease in the amount of wrinkling and disruption of the germinal epithelium was observed after intervention with CUR-n (100 mg/kg). Furthermore, a significant increase in the number of germ cells compared to the group receiving CPZ was detected.
CONCLUSION
This study proposes that CUR-n could be a therapeutic agent for decreasing the adverse effects of MS on testis.
Topics: Male; Animals; Curcumin; Mice; Testis; Disease Models, Animal; Mice, Inbred C57BL; Multiple Sclerosis; Spermatogenesis; Testosterone; Oxidative Stress; Micelles
PubMed: 38778296
DOI: 10.1186/s12906-024-04423-3 -
Bioorganic Chemistry Jul 2024Imaging in the shortwave infrared (SWIR, 1000-1700 nm) region is gaining traction for biomedical applications, leading to an in-depth search for fluorophores emitting...
Imaging in the shortwave infrared (SWIR, 1000-1700 nm) region is gaining traction for biomedical applications, leading to an in-depth search for fluorophores emitting at these wavelengths. The development of SWIR emitters, to be used in vivo in biological media, is mostly hampered by the considerable lipophilicity of the structures, resulting from the highly conjugated scaffold required to shift the emission to this region, that limit their aqueous solubility. In this work, we have modulated a known SWIR emitter, named Flav7, by adding hydrophilic moieties to the flavylium scaffold and we developed a new series of Flav7-derivatives, which proved to be indeed more polar than the parent compound, but still not freely water-soluble. Optical characterization of these derivatives allowed us to select FlavMorpho, a new compound with improved emission properties compared to Flav7. Encapsulation of the two compounds in micelles resulted in water-soluble SWIR emitters, with FlavMorpho micelles being twice as emissive as Flav7 micelles. The SWIR emission extent of FlavMorpho micelles proved also superior to the tail-emission of Indocyanine Green (ICG), the FDA-approved reference cyanine, in the same region, by exciting the probes at their respective absorption maxima in phosphate buffered saline (PBS) solution. The availability of optical imaging devices equipped with lasers able to excite these dyes at their maximum of absorption in the SWIR region, could pave the way for implemented SWIR imaging results.
Topics: Fluorescent Dyes; Drug Design; Molecular Structure; Infrared Rays; Micelles; Optical Imaging; Solubility
PubMed: 38776650
DOI: 10.1016/j.bioorg.2024.107462 -
Biomacromolecules Jun 2024Studying how synthetic polymer assemblies respond to sequential enzymatic stimuli can uncover intricate interactions in biological systems. Using amidase- and...
Studying how synthetic polymer assemblies respond to sequential enzymatic stimuli can uncover intricate interactions in biological systems. Using amidase- and esterase-responsive PEG-based diblock (DBA) and triblock amphiphiles (TBAs), we created two distinct formulations: amidase-responsive DBA with esterase-responsive TBA and vice versa. We studied their cascade responses to the two enzymes and the sequence of their introduction. These formulations underwent cascade mesophase transitions upon the addition of the DBA-degrading enzyme, transitioning from (i) coassembled micelles to (ii) triblock-based hydrogel, and ultimately to (iii) dissolved polymers when exposed to the TBA hydrolyzing enzyme. The specific pathway of the two mesophase transitions depended on the compositions of the formulations and the enzyme introduction sequence. The results highlight the potential for designing polymeric formulations with programmable multistep enzymatic responses, mimicking the complex behavior of biological macromolecules.
Topics: Polyethylene Glycols; Micelles; Esterases; Amidohydrolases; Phase Transition; Polymers; Hydrogels
PubMed: 38776179
DOI: 10.1021/acs.biomac.4c00221 -
Journal of Nanobiotechnology May 2024Transdermal delivery of sparingly soluble drugs is challenging due to their low solubility and poor permeability. Deep eutectic solvent (DES)/or ionic liquid...
BACKGROUND
Transdermal delivery of sparingly soluble drugs is challenging due to their low solubility and poor permeability. Deep eutectic solvent (DES)/or ionic liquid (IL)-mediated nanocarriers are attracting increasing attention. However, most of them require the addition of auxiliary materials (such as surfactants or organic solvents) to maintain the stability of formulations, which may cause skin irritation and potential toxicity.
RESULTS
We fabricated an amphiphilic DES using natural oxymatrine and lauric acid and constructed a novel self-assembled reverse nanomicelle system (DES-RM) based on the features of this DES. Synthesized DESs showed the broad liquid window and significantly solubilized a series of sparingly soluble drugs, and quantitative structure-activity relationship (QSAR) models with good prediction ability were further built. The experimental and molecular dynamics simulation elucidated that the self-assembly of DES-RM was adjusted by noncovalent intermolecular forces. Choosing triamcinolone acetonide (TA) as a model drug, the skin penetration studies revealed that DES-RM significantly enhanced TA penetration and retention in comparison with their corresponding DES and oil. Furthermore, in vivo animal experiments demonstrated that TA@DES-RM exhibited good anti-psoriasis therapeutic efficacy as well as biocompatibility.
CONCLUSIONS
The present study offers innovative insights into the optimal design of micellar nanodelivery system based on DES combining experiments and computational simulations and provides a promising strategy for developing efficient transdermal delivery systems for sparingly soluble drugs.
Topics: Animals; Administration, Cutaneous; Micelles; Solubility; Solvents; Skin Absorption; Skin; Mice; Drug Delivery Systems; Nanoparticles; Quantitative Structure-Activity Relationship; Male; Molecular Dynamics Simulation; Drug Carriers
PubMed: 38773580
DOI: 10.1186/s12951-024-02552-y