Formulation and Comprehensive Evaluation of Biohybrid Hydrogel Membranes Containing Doxycycline or Silver Nanoparticles.

Complicated wounds often require specialized medical treatments, and hydrogels have emerged as a popular choice for wound dressings in such cases due to their unique properties and the ability to incorporate and release therapeutic agents. Our focus was to develop and characterize a new optimized formula for biohybrid hydrogel membranes, which combine natural and synthetic polymers, bioactive natural compounds, like collagen and hyaluronic acid, and pharmacologically active substances (doxycycline or npAg). Dynamic (oscillatory) rheometry confirmed the strong gel-like properties of the obtained hydrogel membranes. Samples containing low-dose DOXY showed a swelling index of 285.68 ± 6.99%, a degradation rate of 71.6 ± 0.91% at 20 h, and achieved a cumulative drug release of approximately 90% at pH 7.4 and 80% at pH 8.3 within 12 h. The addition of npAg influenced the physical properties of the hydrogel membranes. Furthermore, the samples containing DOXY demonstrated exceptional antimicrobial efficacy against seven selected bacterial strains commonly associated with wound infections and complications. Biocompatibility assessments revealed that the samples exhibited over 80% cell viability. However, the addition of smaller-sized nanoparticles led to decreased cellular viability. The obtained biohybrid hydrogel membranes show favorable properties that render them suitable for application as wound dressings.

Exploring the Impact of Alginate-PVA Ratio and the Addition of Bioactive Substances on the Performance of Hybrid Hydrogel Membranes as Potential Wound Dressings.

Healthcare professionals face an ongoing challenge in managing both acute and chronic wounds, given the potential impact on patients' quality of life and the limited availability of expensive treatment options. Hydrogel wound dressings offer a promising solution for effective wound care due to their affordability, ease of use, and ability to incorporate bioactive substances that enhance the wound healing process. Our study aimed to develop and evaluate hybrid hydrogel membranes enriched with bioactive components such as collagen and hyaluronic acid. We utilized both natural and synthetic polymers and employed a scalable, non-toxic, and environmentally friendly production process. We conducted extensive testing, including an in vitro assessment of moisture content, moisture uptake, swelling rate, gel fraction, biodegradation, water vapor transmission rate, protein denaturation, and protein adsorption. We evaluated the biocompatibility of the hydrogel membranes through cellular assays and performed instrumental tests using scanning electron microscopy and rheological analysis. Our findings demonstrate that the biohybrid hydrogel membranes exhibit cumulative properties with a favorable swelling ratio, optimal permeation properties, and good biocompatibility, all achieved with minimal concentrations of bioactive agents.

Nanobodies as Diagnostic and Therapeutic Tools for Cardiovascular Diseases (CVDs).

The aim of this review is to summarize some of the most recent work in the field of cardiovascular disease (CVD) diagnosis and therapy, focusing mainly on the role of nanobodies in the development of non-invasive imaging methods, diagnostic devices, and advanced biotechnological therapy tools. In the context of the increased number of people suffering from CVDs due to a variety of factors such as sedentariness, poor nutrition, stress, and smoking, there is an urgent need for new and improved diagnostic and therapeutic methods. Nanobodies can be easily produced in prokaryotes, lower eukaryotes, and plant and mammalian cells, and offer great advantages. In the diagnosis domain, they are mainly used as labeled probes that bind to certain surface receptors or other target molecules and give important information on the severity and extent of atherosclerotic lesions, using imaging methods such as contrast-enhanced ultrasound molecular imaging (CEUMI), positron emission tomography (PET), single-photon emission computed tomography coupled with computed tomography (SPECT/CT), and PET/CT. As therapy tools, nanobodies have been used either for transporting drug-loaded vesicles to specific targets or as inhibitors for certain enzymes and receptors, demonstrated to be involved in various CVDs.

Binding of flavonoids to yeast aldehyde dehydrogenase: a molecular mechanism and computational approach.

The interaction of three flavonoids, apigenin, fisetin and quercetin with yeast aldehyde dehydrogenase, ALDH was studied by spectroscopic and molecular docking methods. A combination of both static and dynamic processes interaction mechanism for the binding of flavonoids with ALDH was found. The interaction takes place with moderate binding and the interaction was driven by hydrophobic contacts. The microenvironments of the fluorescent amino acids changed upon flavonoids binding. The distances between ALDH and flavonoids determined by Förster Resonant Energy Transfer (FRET) confirmed the results obtained by fluorescence. The structure of ALDH against thermal denaturation was stabilized by apigenin and destabilized by fisetin and quercetin. Molecular docking simulation showed that all flavonoids bind to the same site of ALDH and confirmed the moderate binding straight found in fluorescence.Communicated by Ramaswamy H. Sarma.

New Amorphous Hydrogels with Proliferative Properties as Potential Tools in Wound Healing.

The study and discovery of bioactive compounds and new formulations as potential tools for promoting the repair of dermoepidermal tissue in wound healing is of continuing interest. We have developed a new formulation of amorphous hydrogel based on sodium alginate (NaAlg); type I collagen, isolated by the authors from silver carp tails (COL); glycerol (Gli); Aloe vera gel powder (AV); and silver nanoparticles obtained by green synthesis with aqueous Cinnamomum verum extract (AgNPs@CIN) and vitamin C, respectively. The gel texture of the amorphous hydrogels was achieved by the addition of Aloe vera, demonstrated by a rheological analysis. The evaluations of the cytotoxicity and cell proliferation capacity of the experimental amorphous hydrogels were performed against human foreskin fibroblast Hs27 cells (CRL-1634-ATCC). The developed gel formulations did not show a cytotoxic effect. The hydrogel variant containing AgNPs@CIN in a concentration of 8 µg Ag/gel formulation and hydrogel variant with vitamin C had proliferative activity. In addition, the antibacterial activity of the hydrogels was evaluated against S. aureus ATCC 6538, Ps. aeruginosa ATCC 27853, and E. coli ATCC 25922. The results demonstrated that the gel variant based on AgNPs@CIN in a concentration of 95 µg Ag/gel formulation and the hydrogel based on vitamin C show antibacterial activity. Therefore, the developed hydrogels with AgNPs@CIN and vitamin C could be promising alternatives in wound healing.

Sensor-based gait analysis in the premotor stage of LRRK2 G2019S-associated Parkinson's disease.

INTRODUCTION: There is a need for biomarkers to monitor the earliest phases of Parkinson's disease (PD), especially in premotor stages. Here, we studied whether there are early gait alterations in carriers of the G2019S mutation of LRRK2 that can be detected by means of an inertial sensor system. METHODS: Twenty-one idiopathic PD patients, 20 LRRK2-G2019S PD, 27 asymptomatic carriers of LRRK2-G2019S mutation (AsG2019S) and 36 controls walked equipped with 16 lightweight inertial sensors in three different experiments: i/normal gait, ii/fast gait and iii/dual-task gait. In the AsG2019S group, DaT-SPECT (123I-ioflupane) with semi-quantitative analysis was carried out. Motor and cognitive performance were evaluated using MDS-UPDRS-III and MoCA scales. We employed neural network techniques to classify individuals based on their walking patterns. RESULTS: PD patients and controls showed differences in speed, stride length and arm swing amplitude, variability and asymmetry in all three tasks (p < 0.01). In the AsG2019S group, the only differences were detected during fast walking, with greater step time on the non-dominant side (p < 0.05), lower step/stride time variability (p < 0.01) and lower step time asymmetry (p < 0.01). DaT uptake showed a significant correlation with step time during fast walking on the non-dominant side (r = -0.52; p < 0.01). The neural network was able to differentiate between AsG2019S and healthy controls with an accuracy rate of 82.5%. CONCLUSION: Our sensor-based analysis did not detect substantial and robust changes in the gait of LRRK2-G2019S asymptomatic mutation carriers. Nonetheless, step or stride time during fast walking, supported by the observed correlation with striatal DaT binding deserves consideration as a potential biomarker in future studies.

Natural Compounds With Antimicrobial and Antiviral Effect and Nanocarriers Used for Their Transportation.

Due to the increasing prevalence of life-threatening bacterial, fungal and viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compunds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable compounds for this task are usually derived from natural sources (animal, plant or even microbial). In this review article, the latest and most promising natural compounds used to combat bacteria, filamentous fungi and viruses are presented and evaluated. These include plant extracts, essential oils, small antimicrobial peptides of animal origin, bacteriocins and various groups of plant compounds (triterpenoids; alkaloids; phenols; flavonoids) with antimicrobial and antiviral activity. Data are presented on the inhibitory activity of each natural antimicrobial substance and on the putative mechanism of action against bacterial and fungal strains. The results show that among the bioactive compounds studied, triterpenoids have significant inhibitory activity against coronaviruses, but flavonoids have also been shown to inhibit SARS-COV-2. The last chapter is devoted to nanocarriers used to improve stability, bioavailability, cellular uptake/internalization, pharmacokinetic profile and reduce toxicity of natural compunds. There are a number of nanocarriers such as liposomes, drug delivery microemulsion systems, nanocapsules, solid lipid nanoparticles, polymeric micelles, dendrimers, etc. However, some of the recent studies have focused on the incorporation of natural substances with antimicrobial/antiviral activity into polymeric nanoparticles, niosomes and silver nanoparticles (which have been shown to have intrinsic antimicrobial activity). The natural antimicrobials isolated from animals and microorganisms have been shown to have good inhibitory effect on a range of pathogens, however the plants remain the most prolific source. Even if the majority of the studies for the biological activity evaluation are in silico or in vitro, their internalization in the optimum nanocarriers represents the future of "green therapeutics" as shown by some of the recent work in the field.

The influence of sugar-protein complexes on the thermostability of C-reactive protein (CRP).

The purpose of the present study was to evaluate de influence of protein-sugar complexation on the stability and functionality of C-reactive protein, after exposure to constant high temperatures, in order to develop highly stable positive controls for in-vitro diagnostic tests. C-reactive protein is a plasmatic protein used as a biomarker for the diagnosis of a series of health problems such as ulcerative colitis, cardiovascular diseases, metabolic syndrome, due to its essential role in the evolution of chronic inflammation. The sugar-protein interaction was investigated using steady state and time resolved fluorescence. The results revealed that there are more than two classes of tryptophan, with different degree of accessibility for the quencher molecule. Our study also revealed that sugar-protein complexes have superior thermostability, especially after gamma irradiation at 2 kGy, the protein being stable and functional even after 22 days exposure to 40 °C.

Wound healing applications of creams and "smart" hydrogels.

Although superficial wounds are often easy to treat for healthy individuals, there are some more severe types of wounds (burns, ulcers, diabetic wounds, etc.) that are a challenge for clinicians. A good therapeutic result is based on the delivery of a treatment at the right time, for the right patient. Our goal was to sum up useful knowledge regarding wound healing and wound treatments, based on creams and hydrogels with various active ingredients. We concluded that both preparations have application in preventing infections and promoting healing, but their efficacy is clearly conditioned by the type, depth, severity of the wound and patient profile. However, due to their superior versatility and capability of maintaining the integrity and functionality of the active ingredient, as well as it is controlled release at site, hydrogels are more suited for incorporating different active ingredients. New wound healing devices can combine smart hydrogel dressings with physical therapies to deliver a more efficient treatment to patients if the indications are appropriate.

Platform with biomimetic electrochemical sensors for adiponectin and leptin detection in human serum.

Two new biomimetic sensors for the detection of adiponectin (A) and leptin (L) through molecularly imprinted polymers (MIPs) onto gold working electrodes (GWEs) were fabricated. Based on electrochemical impedance spectroscopy (EIS) results and cyclic voltammetry (CV) characteristics recorded in the development stages of the fabricated sensors, the sensors were electrochemically optimized and used in an integrated microfluidic platform to detect adiponectin/leptin via conductance signals and non-imprinted electrodes were used as references. To overcome the limitation of the low response signals after template binding non-conductive polyphenol (PP) and poliscopoletin (PS) were used for templates formation. Under optimized experimental conditions the conductance and resistance signals were obtained in the linear range of 0-50 µg ml-1 for A and 1-32 ng∙ml-1 for L with low limits of detection (0.25 µg ml-1 for A and 0.110 ng ml-1 for L). The dedicated platform exhibited an excellent response with great selectivity and stability. Finally, the proposed biomimetic sensors were successfully applied to enable the determination of A and L in human patient's serum with very high accuracy when compared to enzyme-linked immunosorbent assay ELISA reference methods.