Development of a Novel Human Serum Albumin-Based Tool for Effective Drug Discovery: The Investigation of Protein Quality and Immobilization.

The binding ability of human serum albumin (HSA) on active pharmaceutical ingredients (APIs) is one of the most important parameters in the early stages of drug discovery. In this study, an immobilized HSA-based tool was developed for the rapid and easy in vitro screening of API binding. The work explored the serious incompleteness in the identification of HSA used for in vitro screening published in the last five years.

Effect of Mo and W underlayers on ordered phase formation in Fe-Au-Pd multilayer thin films at low temperatures.

Fe-Pd based thin films with Au intermediate layer fabricated on different substrates (SiO, SiO/Mo, SiO/W) were investigated at annealing temperatures up to 460 °C. The samples were deposited by magnetron sputtering and were post-annealed in vacuum. The ongoing processes were investigated by chemical depth profiling and X-ray diffraction.

Development of Innovative Electrospun Nepafenac-Loaded Nanofibers-based Ophthalmic Inserts.

Electrospun nanofibers can be utilized to develop patient-centric ophthalmic formulations with reasonable bioavailability at the targeted site. The current study aimed to develop 0.1% w/w of nepafenac-loaded electrospun nanofibrous webs as potential candidates for ocular delivery of nepafenac with improved solubility and stability.

Serum Albumin in Nasal Drug Delivery Systems: Exploring the Role and Application.

The application of serum albumin in various types of formulations has emerged as a valuable option in biomedical research, especially in the field of nasal drug delivery systems. A serum albumin-based carrier system has been employed due to several benefits, such as enhancing drug solubility and stability, generating the desired controlled release profile, and developing favorable properties with respect to the challenges in nasal conditions, which, in this case, involves hindering rapid elimination due to nasal mucociliary clearance. Accordingly, considering the important role of serum albumin, in-depth knowledge related to its utilization in preparing nasal drug formulation is highly encouraged.

The effect of mucoadhesive polymers on ocular permeation of thermoresponsive in situ gel containing dexamethasone-cyclodextrin complex.

Dexamethasone (DXM) is a commonly used corticosteroid in the treatment of ocular inflammatory conditions that affect more and more people. The aim of this study was to evaluate the effect of the combination of hydroxypropyl-β-cyclodextrin (HPBCD), in situ gelling formulations, and other mucoadhesive polymers, i.e.

Bivalent chromatin accommodates survivin and BRG1/SWI complex to activate DNA damage response in CD4 cells.

Background: Bivalent regions of chromatin (BvCR) are characterized by trimethylated lysine 4 (H3K4me3) and lysine 27 on histone H3 (H3K27me3) deposition which aid gene expression control during cell differentiation. The role of BvCR in post-transcriptional DNA damage response remains unidentified. Oncoprotein survivin binds chromatin and mediates IFNγ effects in CD4 cells.

Mucoadhesive in situ nasal gel of amoxicillin trihydrate for improved local delivery: Ex vivo mucosal permeation and retention studies.

Orally administered amoxicillin is recommended as the first-line treatment of acute bacterial rhinosinusitis (ABR) and given in a high-dose regimen. However, the risk of various systemic adverse reactions and low oral bioavailability are unbearable, increasing the threat of antibiotic resistance. Therefore, nasal delivery of amoxicillin can be a potential approach for effectively treating ABR locally, as well as overcoming those drawbacks.

A Stereolithography-Based Modified Spin-Casting Method for Faster Laboratory-Scale Production of Dexamethasone-Containing Dissolving Microneedle Arrays.

Microneedle arrays (MNAs) consist of a few dozens of submillimeter needles, which tend to penetrate through the stratum corneum layer of the skin and deliver hardly penetrating drugs to the systemic circulation. The application of this smart dosage form shows several advantages, such as simple use and negligible pain caused by needle punctures compared to conventional subcutaneous injections. Dissolving MNAs (DMNAs) represent a promising form of cutaneous drug delivery due to their high drug content, biocompatibility, and ease of use.

Comparative Study of TPGS and Soluplus Polymeric Micelles Embedded in Poloxamer 407 In Situ Gels for Intranasal Administration.

This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic options are required. Dexamethasone was encapsulated into three different polymeric micelle formulations: Soluplus or TPGS-only and their mixed combinations.

Cardiac Sarcoidosis: A Comprehensive Clinical Review.

Sarcoidosis is an inflammatory multisystemic disease of unknown etiology characterized by the formation of non-caseating granulomas. Sarcoidosis can affect any organ, predominantly the lungs, lymphatic system, skin and eyes. While 90% of patients with sarcoidosis have lung involvement, an estimated 5% of patients with sarcoidosis have clinically manifest cardiac sarcoidosis (CS), whereas approximately 25% have asymptomatic, clinically silent cardiac involvement verified by autopsy or imaging studies.

Exploring Vacuum Compression Molding as a Preparation Method for Flexible-Dose Pediatric Orodispersible Films.

In recent years, solid dosage forms have gained interest in pediatric therapy because they can provide valuable benefits in terms of dose accuracy and stability. Particularly for orodispersible films (ODFs), the literature evidences increased acceptability and dose flexibility. Among the various available technologies for obtaining ODFs, such as solvent casting, hot-melt extrusion, and ink printing technologies, the solvent-free preparation methods exhibit significant advantages.

Appraising protein conformational changes by resampling time-resolved serial x-ray crystallography data.

With the development of serial crystallography at both x-ray free electron laser and synchrotron radiation sources, time-resolved x-ray crystallography is increasingly being applied to study conformational changes in macromolecules. A successful time-resolved serial crystallography study requires the growth of microcrystals, a mechanism for synchronized and homogeneous excitation of the reaction of interest within microcrystals, and tools for structural interpretation. Here, we utilize time-resolved serial femtosecond crystallography data collected from microcrystals of bacteriorhodopsin to compare results from partial occupancy structural refinement and refinement against extrapolated data.

Monitoring correlates of SARS-CoV-2 infection in cell culture using a two-photon-active calcium-sensitive dye.

Background: The organism-wide effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection are well studied, but little is known about the dynamics of how the infection spreads in time among or within cells due to the scarcity of suitable high-resolution experimental systems. It has been reported that SARS-CoV-2 infection pathways converge at calcium influx and subcellular calcium distribution changes. Imaging combined with a proper staining technique is an effective tool for studying subcellular calcium-related infection and replication mechanisms at such resolutions.

The evolution of exceptional diversity in parental care and fertilization modes in ray-finned fishes.

Among vertebrates, ray-finned fishes (Actinopterygii) display the highest diversity in parental care, and their diversification has been hypothesized to be related to phylogenetic changes in fertilization modes. Using the most comprehensive, sex-specific data from 7,600 species of 62 extant orders of ray-finned fishes, we inferred ancestral states and transitions among care types and caring episodes (i.e.

Risperidone-Loaded Nasal Thermosensitive Polymeric Micelles: Quality by Design-Based Formulation Study.

The current research aims to develop thermosensitive polymeric micelles loaded with risperidone for nasal administration, emphasizing the added benefits of their thermosensitive behavior under nasal conditions. An initial risk assessment facilitated the advanced development process, confirming that the key indicators of thermosensitivity were suitable for nasal application. The polymeric micelles exhibited an average size of 118.

The structure of the second CysD domain of MUC2 and role in mucin organization by transglutaminase-based cross-linking.

The MUC2 mucin protects the colonic epithelium by a two-layered mucus with an inner attached bacteria-free layer and an outer layer harboring commensal bacteria. CysD domains are 100 amino-acid-long sequences containing 10 cysteines that separate highly O-glycosylated proline, threonine, serine (PTS) regions in mucins. The structure of the second CysD, CysD2, of MUC2 is now solved by nuclear magnetic resonance.

Immobilization of human tyrosine hydroxylase onto magnetic nanoparticles - A novel formulation of a therapeutic enzyme.

Human tyrosine hydroxylase (hTH) has key role in the production of catecholamine neurotransmitters. The structure, function and regulation of hTH has been extensively researched area and the possibility of enzyme replacement therapy (ERT) involving hTH through nanocarriers has been raised as well. However, our understanding on how hTH may interact with nanocarriers is still lacking.

Not all apparently gynandromorphic butterflies are gynandrous: The case of Polyommatus icarus and its relatives (Lepidoptera: Lycaenidae).

Beside the more than two thousand normal specimens of Polyommatus icarus (Rottemburg, 1775) yielded by rearing experiments, there was one perfectly bilateral dichromatic individual first considered to be gynandrous. On the basis of analysing genitalia traits, wing surface covering scale micromorphology, and the spectral characteristics of the blue colour generated by the cover scales, the gender of the specimen has been identified as female. This exemplar was investigated in comparison with gynandrous specimens from the collections of the Hungarian Natural History Museum exhibiting various degrees of intermixing of blue and brown coloration.

Essential considerations towards development of effective nasal antibiotic formulation: features, strategies, and future directions.

Introduction: Intranasal antibiotic products are gaining popularity as a promising method of administering antibiotics, which provide numerous benefits, e.g. enhancing drug bioavailability, reducing adverse effects, and potentially minimizing resistance threats.

Correlations between the anti-corrosion properties and the photocatalytic behavior of epoxy coatings incorporating modified graphene oxide deposited on a zinc substrate.

This research aimed to create a substrate-coating system based on zinc and an epoxy resin incorporating modified graphene oxide, which possesses two key characteristics: effective resistance against corrosion and the ability to harness photocatalytic properties. Furthermore, correlations between the anti-corrosion properties and the photocatalytic behaviour of the coatings were made. Thin epoxy (EP) layers embedding 0.

A Molecular Hybrid of the GFP Chromophore and 2,2'-Bipyridine: An Accessible Sensor for Zn Detection with Fluorescence Microscopy.

The few commercially available chemosensors and published probes for in vitro Zn detection in two-photon microscopy are compromised by their flawed spectroscopic properties, causing issues in selectivity or challenging multistep syntheses. Herein, we present the development of an effective small molecular GFP chromophore-based fluorescent chemosensor with a 2,2'-bipyridine chelator moiety (GFZnP BIPY) for Zn detection that has straightforward synthesis and uncompromised properties. Detailed experimental characterizations of the free and the zinc-bound compounds within the physiologically relevant pH range are presented.

A GFP Inspired 8-Methoxyquinoline-Derived Fluorescent Molecular Sensor for the Detection of Zn by Two-Photon Microscopy.

An effective, GFP-inspired fluorescent Zn sensor is developed for two-photon microscopy and related biological application that features an 8-methoxyquinoline moiety. Excellent photophysical characteristics including a 37-fold fluorescence enhancement with excitation and emission maxima at 440 nm and 505 nm, respectively, as well as a high two-photon cross-section of 73 GM at 880 nm are reported. Based on the experimental data, the relationship between the structure and properties was elucidated and explained backed up by DFT calculations, particularly the observed PeT phenomenon for the turn-on process.

A Comparative Pharmacokinetic Study for Cysteamine-Containing Eye Drops as an Orphan Topical Therapy in Cystinosis.

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of "gold dust" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age.