Gelatin and gelatin/starch-based films modified with sorbitol for wound healing.

Gelatin-based films modified with sorbitol were produced from gelatin solution or gelatin/starch blends using a simple and low-cost solvent casting method, and subsequently, their physicochemical, mechanical, and biocompatibility properties were characterized. This work focused on developing and optimizing a biopolymeric blend to improve the pure biopolymers' properties for potential biomedical applications such as wound dressing. The films were characterized in terms of morphology and transparency, mechanical, moisture and swelling properties, thermal stability, and degradation potential. Moreover, hemocompatibility, as well as cytocompatibility of prepared films, were examined. The addition of sorbitol contributed to improving mechanical properties, swelling reduction, and increasing biostability over time. The cytocompatibility of obtained films was confirmed in vitro with two different human cell lines, fibroblastic and osteoblastic, and a more favorable cellular response was received for fibroblasts. Further, in hemocompatibility studies, it was found that all films may be classified as non-hemolytic as they did not have a negative effect on the human erythrocytes. The obtained results indicate the great potential of the gelatin/starch blends modified with sorbitol as regenerative biomaterials intended for wound healing applications.

Modification of the Human Amniotic Membrane Using Different Cross-Linking Agents as a Promising Tool for Regenerative Medicine.

Human amniotic membranes (hAMs) obtained during cesarean sections have proven to be clinically useful as an interesting biomaterial in a wide range of tissue engineering applications such as ocular surface reconstruction, burn treatments, chronic wounds, or bedsore ulcers. It presents antimicrobial properties, promotes epithelization, reduces inflammation and angiogenesis, contains growth factors, and constitutes the reservoir of stem cells. However, variability in hAM stiffness and its fast degradation offers an explanation for the poor clinical applications and reproducibility. In addition, the preparatory method of hAM for clinical use can affect its mechanical properties, and these differences can influence its application. As a directly applied biomaterial, the hAM should be available in a ready-to-use manner in clinical settings. In the present study, we performed an analysis to improve the mechanical properties of hAM by the addition of various reagents used as protein cross-linkers: EDC/NHS, PEG-dialdehyde, PEG-NHS, dialdehyde starch, and squaric acid. The effect of hAM modification using different cross-linking agents was determined via infrared spectroscopy, thermal analyses, mechanical properties analyses, enzymatic degradation, and cytotoxicity tests. The use of PEG-dialdehyde, PEG-NHS, dialdehyde starch, and squaric acid increases the mechanical strength and elongation at the breaking point of hAM, while the addition of EDC/NHS results in material stiffening and shrinkage. Also, the thermal stability and degradation resistance were evaluated, demonstrating higher values after cross-linking. Overall, these results suggest that modification of human amniotic membrane by various reagents used as protein cross-linkers may make it easier to use hAM in clinical applications, and the presented study is a step forward in the standardization of the hAM preparation method.

Gender Differences in Post-Operative Human Skin.

Although the impact of age, gender, and obesity on the skin wound healing process has been extensively studied, the data related to gender differences in aspects of skin scarring are limited. The present study performed on abdominal human intact and scar skin focused on determining gender differences in extracellular matrix (ECM) composition, dermal white adipose tissue (dWAT) accumulation, and Foxn1 expression as a part of the skin response to injury. Scar skin of men showed highly increased levels of COLLAGEN 1A1, COLLAGEN 6A3, and ELASTIN mRNA expression, the accumulation of thick collagen I-positive fibers, and the accumulation of α-SMA-positive cells in comparison to the scar skin of women. However, post-injured skin of women displayed an increase (in comparison to post-injured men's skin) in collagen III accumulation in the scar area. On the contrary, women's skin samples showed a tendency towards higher levels of adipogenic-related genes (PPARγ, FABP4, LEPTIN) than men, regardless of intact or scar skin. Intact skin of women showed six times higher levels of LEPTIN mRNA expression in comparison to men intact (p < 0.05), men post-injured (p < 0.05), or women post-injured scar (p < 0.05) skin. Higher levels of FOXN1 mRNA and protein were also detected in women than in men's skin. In conclusion, the present data confirm and extend (dWAT layer) the data related to the presence of differences between men and women in the skin, particularly in scar tissues, which may contribute to the more effective and gender-tailored improvement of skin care interventions.

Dermal white adipose tissue development and metabolism: The role of transcription factor Foxn1.

Intradermal adipocytes form dermal white adipose tissue (dWAT), a unique fat depot localized in the lower layer of the dermis. However, recognition of molecular factors regulating dWAT development, homeostasis, and bioactivity is limited. Using Foxn1-/- and Foxn1+/+ mice, we demonstrated that epidermally expressed Foxn1 regulates dWAT development and defines the adipogenic capacity of dermal fibroblasts. In intact and post-wounded skin, Foxn1 contributes to the initial stimulation of dWAT adipogenesis and participates in the modulation of lipid metabolism processes. Furthermore, Foxn1 activity strengthens adipogenic processes through Bmp2 and Igf2 signaling and regulates lipid metabolism in differentiated dermal fibroblasts. The results reveal the contribution of Foxn1 to dWAT metabolism, thus identifying possible targets for modulation and regulation of dWAT in physiological and pathological processes in the skin.

Cu-HKUST-1 and Hydroxyapatite-The Interface of Two Worlds toward the Design of Functional Materials Dedicated to Bone Tissue Regeneration.

A novel composite based on biocompatible hydroxyapatite (HA) nanoparticles and Cu-HKUST-1 (Cu-HKUST-1@HA) has been prepared following a layer-by-layer strategy. Cu-HKUST-1 was carefully selected from a group of four Cu-based metal-organic frameworks as the material with the most promising antimicrobial activity. The formation of a colloidal Cu-HKUST-1 layer on HA nanoparticles was confirmed by various techniques, e.g., infrared spectroscopy, powder X-ray diffraction, N2 sorption, transmission electron microscopy imaging, electron paramagnetic resonance, and X-ray absorption spectroscopy. Importantly, such a Cu-HKUST-1 layer significantly improved the nanomechanical properties of the composite, with Young's modulus equal to that of human cortical bone (13.76 GPa). At the same time, Cu-HKUST-1@HA has maintained the negative zeta potential (-16.3 mV in pH 7.4) and revealed biocompatibility toward human dermal fibroblasts up to a concentration of 1000 µg/mL, without inducing ex vivo hemolysis. Chemical stability studies of the composite over 21 days in a buffer-simulated physiological fluid allowed a detailed understanding of the transformations that the Cu-HKUST-1@HA undergoes over time. Finally, it has been confirmed that the Cu-HKUST-1 layer provides antibacterial properties to HA, and the synergism reached in this way makes it promising for bone tissue regeneration.

Activation of Ethanol Transformation on Copper-Containing SBA-15 and MnSBA-15 Catalysts by the Presence of Oxygen in the Reaction Mixture.

The aim of this study was to get insight into the pathway of the acetaldehyde formation from ethanol (the rate-limiting step in the production of 1,3-butadiene) on Cu-SBA-15 and Cu-MnSBA-15 mesoporous molecular sieves. Physicochemical properties of the catalysts were investigated by XRD, N2 ads/des, Uv-vis, XPS, EPR, pyridine adsorption combined with FTIR, 2-propanol decomposition and 2,5-hexanedione cyclization and dehydration test reactions. Ethanol dehydrogenation to acetaldehyde (without and with oxygen) was studied in a flow system using the FTIR technique. In particular, the effect of Lewis acid and basic (Lewis and BrØnsted) sites, and the oxygen presence in the gas reaction mixture with ethanol on the activity and selectivity of copper catalysts, was assessed and discussed. Two different reaction pathways have been proposed depending on the reaction temperature and the presence or absence of oxygen in the flow of the reagents (via ethoxy intermediate way at 593 K, in ethanol flow, or ethoxide intermediate way at 473 K in the presence of ethanol and oxygen in the reaction mixture).

Specific expression of alternatively spliced genes in the turkey (Meleagris gallopavo) reproductive tract revealed their function in spermatogenesis and post-testicular sperm maturation.

The tissue-specific profile of alternatively spliced genes (ASGs) and their involvement in reproduction processes characteristic of turkey testis, epididymis, and ductus deferens were investigated for the first time in birds. Deep sequencing of male turkey reproductive tissue RNA samples (n = 6) was performed using Illumina RNA-Seq with 2 independent methods, rMATs and SUPPA2, for differential alternative splicing (DAS) event prediction. The expression of selected ASGs was validated using quantitative real-time reverse transcriptase-polymerase chain reaction. The testis was found to be the site of the highest number of posttranscriptional splicing events within the reproductive tract, and skipping exons were the most frequently occurring class of alternative splicing (AS) among the reproductive tract. Statistical analysis revealed 86, 229, and 6 DAS events in the testis/epididymis, testis/ductus deferens, and epididymis/ductus deferens comparison, respectively. Alternative splicing was found to be a mechanism of gene expression regulation within the turkey reproduction tract. In testis, modification was observed for spermatogenesis specific genes; the changes in 5' UTR could act as regulator of MEIG1 expression (a player during spermatocytes meiosis), and modification of 3' UTR led to diversification of CREM mRNA (modulator of gene expression related to the structuring of mature spermatozoa). Sperm tail formation can be regulated by changes in the 5' UTR of testicular SLC9A3R1 and gene silencing by producing dysfunctional variants of ODF2 in the testis and ATP1B3 in the epididymis. Predicted differentially ASGs in the turkey reproductive tract seem to be involved in the regulation of spermatogenesis, including acrosome formation and sperm tail formation and binding of sperm to the zona pellucida. Several ASGs were classified as cilia by actin and microtubule cytoskeleton organization. Such genes may play a role in the organization of sperm flagellum and post-testicular motility development. To our knowledge, this is the first functional investigation of alternatively spliced genes associated with tissue-specific processes in the turkey reproductive tract.

Structural Diversity, XAS and Magnetism of Copper(II)-Nickel(II) Heterometallic Complexes Based on the [Ni(NCS)6]4- Unit.

The new heterometallic compounds, [{Cu(pn)2}2Ni(NCS)6]n·2nH2O (1), [{CuII(trien)}2Ni(NCS)6CuI(NCS)]n (2) and [Cu(tren)(NCS)]4[Ni(NCS)6] (3) (pn = 1,2-diaminopropane, trien = triethylenetetramine and tren = tris(2-aminoethylo)amine), were obtained and characterized by X-ray analysis, IR spectra, XAS and magnetic measurements. Compounds 1, 2 and 3 show the structural diversity of 2D, 1D and 0D compounds, respectively. Depending on the polyamine used, different coordination polyhedron for Cu(II) was found, i.e., distorted octahedral (1), square pyramidal (2) and trigonal bipyramidal (3), whereas coordination polyhedron for nickel(II) was always octahedral. It provides an approach for tailoring magnetic properties by proper selection of auxiliary ligands determining the topology. In 1, thiocyanate ligands form bridges between the copper and nickel ions, creating 2D layers of sql topology with weak ferromagnetic interactions. Compound 2 is a mixed-valence copper coordination polymer and shows the rare ladder topology of 1D chains decorated with [CuII(tren)]2+ antennas as the side chains attached to nickel(II). The ladder rails are formed by alternately arranged Ni(II) and Cu(I) ions connected by N2 thiocyanate anions and rungs made by N3 thiocyanate. For the Cu(I) ions, the tetrahedral thiocyanate environment mixed N/S donor atoms was found, confirming significant coordination spheres rearrangement occurring at the copper precursor together with the reduction in some Cu(II) to Cu(I). Such topology enables significant simplification of the magnetic properties modeling by assuming magnetic coupling inside {NiIICuII2} trinuclear units separated by diamagnetic [Cu(NCS)(SCN)3]3- linkers. Compound 3 shows three discrete mononuclear units connected by N-H…N and N-H…S hydrogen bonds. Analysis of XAS proves that the average ligand character and the covalency of the unoccupied metal d-based orbitals for copper(II) and nickel(II) increase in the following order: 1 → 2 → 3. In 1 and 2, a weak ferromagnetic coupling between copper(II) and nickel(II) was found, but in 2, additional and stronger antiferromagnetic interaction between copper(II) ions prevailed. Compound 3, as an ionic pair, shows, as expected, a spin-only magnetic moment.

Populations of NK Cells and Regulatory T Cells in the Endometrium of Cycling Mares-A Preliminary Study.

Endometrial immune cells are essential to support uterine functions across the estrous cycle and in preparation for pregnancy. It has been acknowledged that changes in phenotype and/or numbers of lymphocytes, such as regulatory T cells (Tregs) and NK cells, might result in lower fertility in women and mice. Little is known about equine endometrial immune cells across the estrous cycle. Here, we compared the populations of endometrial Tregs and NK cells in estrus and diestrus in mares. Endometrial biopsy and blood samples were taken in estrus and diestrus from 11 mares ages 4-12 years. Flow cytometry with anti-CD4, -CD25 and -FOXP3 and anti-NKp46 and -CD3 antibodies was used to determine the populations of Tregs and NK cells, respectively. The concentration of progesterone was measured with chemiluminescence immunoassay. The results were analyzed with paired Student t tests. The mean percentage of endometrial CD4+FOXP3+ Tregs was 13.7 ± 6.2% in diestrus and 14.5 ± 5.9% in estrus, while the mean percentage of endometrial CD4+FOXP3+CD25+ Tregs changed from 3.6 ± 2.1% in diestrus to 2 ± 2% in estrus (p = 0.0947). The mean proportion of CD3-NKp46+ lymphocytes in the endometrium was not significantly different, with 6 ± 1% in estrus and 6.5 ± 1.4% in diestrus. There was a large variation in the percentage of NK cells between mares of 2.1-12.7%. This study showed, for the first time, the presence of CD4+FOXP3+CD25+ Tregs and CD3-NKp46+ NK cells in the endometrium of non-pregnant cycling mares. The percentage of Tregs, and to a greater extent NK cells, showed large fluctuations between mares. Both Tregs and NK cells might be important for the preparation of the endometrium for semen deposition and pregnancy; however, further research is required.

Hypoxia reveals a new function of Foxn1 in the keratinocyte antioxidant defense system.

Skin exposed to environmental threats, including injuries and oxidative stress, develops an efficient but not fully recognized system of repair and antioxidant protection. Here, using mass spectrometry analysis (LC-MS/MS), followed by in vitro and in vivo experiments, we provided evidence that Foxn1 in keratinocytes regulates elements of the electron transport chain and participates in the thioredoxin system (Txn2, Txnrd3, and Srxn1) induction, particularly in a hypoxic environment. We first showed that Foxn1 in keratinocytes upregulates glutathione thioredoxin reductase 3 (Txnrd3) protein expression, and high levels of Txnrd3 mRNA were detected in injured skin of Foxn1+/+ mice. We also showed that Foxn1 strongly downregulated the Ccn2 protein expression, participating in epidermal reconstruction after injury. An in vitro assay revealed that Foxn1 controls keratinocyte migration, stimulating it under normoxia and suppressing it under hypoxia. Keratinocytes overexpressing Foxn1 and exposed to hypoxia displayed a reduced ability to promote angiogenesis by downregulating Vegfa expression. In conclusion, this study showed a new mechanism in which Foxn1, along with hypoxia, participates in the activation of antioxidant defense and controls the functional properties of keratinocytes.

Comparative studies on the effect of pig adipose-derived stem cells (pASCs) preconditioned with hypoxia or normoxia on skin wound healing in mice.

Adipose-derived stem cells (ASCs) from human and animal fat have emerged as therapeutic alternatives for damaged tissues. Pre-conditioning of ASCs with hypoxia results in their functional enhancement, which might facilitate the process of healing. However, there is still a critical need for large-scale preclinical studies to reinforce the translation of these findings into clinical practice for humans and in veterinary medicine. Here, we adapted a full-thickness excisional skin wound mouse model to evaluate and compare the effect of pig adipose-derived stem cells (pASCs) cultured under normoxia (pASCs-Nor) or hypoxia (pASCs-Hyp) on the healing process. We show that pASCs-Hyp accelerated re-epithelialization, increased hyaluronic acid (HA) content, and decreased scar elevation index (SEI) during the late stage of healing (day 21). Transplantation of pASCs-Hyp also promoted expression of angiogenic marker VegfA and decreased levels of pro-scarring Tgfß1. Mice tolerated xenotransplantation of the pASCs with no impact on macrophage (CD68 -positive cell) content. However, wounds treated with pASCs-Hyp exhibited decreased elasticity at the early stage of healing and increased expression of Wnt signaling members including Wnt10a, Wnt11, and ß-catenin, which are associated with scar-forming wound repair. In conclusion, pASCs treatment may provide a critical step toward the evaluation of pASCs as therapeutically relevant cells in the context of wound healing.

Sawhorse-type ruthenium complexes with triazolopyrimidine ligands - what do they represent in terms of cytotoxic and CORM compounds?

Three sawhorse-type ruthenium(I) complexes containing purine analogs such as triazolopyrimidines of the general formula [Ru2(CO)4(µ-OOCCH3)2(L)2], where L is 1,2,4-triazolo[1,5-a]pyrimidine (tp for 1), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp for 2) and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp for 3), have been synthesized and characterized by elemental analysis, infrared analysis, multinuclear magnetic resonance spectroscopic techniques (1H, 13C, 15N), and single-crystal X-ray diffraction (for 1 and 2). By assay with myoglobin, the photo-activated CO-releasing molecule (PhotoCORM) character of (1-3) has been confirmed, thus indicating the possibility of use in CO-based therapies. The importance of UV-induced modification has been investigated in the context of anticancer properties. Complexes (1) and (2) have been thoroughly screened for their in vitro cytotoxicity against various cancer cell lines: MCF-7 (breast cancer), HeLa (cervical cancer) and C32 (melanoma), as well as L929 normal fibroblasts in the dark and presence of UV-A light (365 nm). The results were compared with those for cisplatin and two reference ruthenium complexes, namely NAMI-A and KP1019. The most hydrophilic [Ru2(CO)4(µ-OOCCH3)2(tp)2] (1) (log P = -1.12) was found to be more cytotoxic than (2), despite the lower cellular uptake measured by ICP-MS toward HeLa cells. Importantly, photo-induced stimulation of cells with (1) resulted in a lower decrease in the viability of L929 normal cells (IC50 = 154.7 ± 6.5 µM) in comparison with HeLa cancer cells (IC50 = 66.7 ± 3.4 µM). The photo-induced stimulation of (1) and (2) increases ROS generation, and their anticancer activity may be a partially ROS-dependent phenomenon.

Urinary bladder augmentation with acellular biologic scaffold-A preclinical study in a large animal model.

Current strategies in urinary bladder augmentation include use of gastrointestinal segments, however, the technique is associated with inevitable complications. An acellular biologic scaffold seems to be a promising option for urinary bladder augmentation. The aim of this study was to evaluate the utility of bladder acellular matrix (BAM) for reconstruction of clinically significant large urinary bladder wall defects in a long-term porcine model. Urinary bladders were harvested from 10 pig donors. Biological scaffolds were prepared by chemically removing all cellular components from urinary bladder tissue. A total of 10 female pigs underwent hemicystectomy and subsequent bladder reconstruction with BAM. The follow-up study was 6 months. Reconstructed bladders were subjected to radiological, macroscopic, histological, immunohistochemical, and molecular evaluations. Six out of ten animals survived the 6-month follow-up period. Four pigs died during observation due to mechanical failure of the scaffold, anastomotic dehiscence between the scaffold and native bladder tissue, or occluded catheter. Tissue engineered bladder function was normal without any signs of postvoid residual urine in the bladder or upper urinary tracts. Macroscopically, graft shrinkage was observed. Urothelium completely covered the luminal surface of the graft. Smooth muscle regeneration was observed mainly in the peripheral graft region and gradually decreased toward the center of the graft. Expression of urothelial, smooth muscle, blood vessel, and nerve markers were lower in the reconstructed bladder wall compared to the native bladder. BAM seems to be a promising biomaterial for reconstruction of large urinary bladder wall defects. Further research on cell-seeded BAM to enhance urinary bladder regeneration is required.

Health-related Quality of Life after a one-year follow-up of patients undergoing endovascular leg revascularization.

BACKGROUND: Lower limb revascularization not only improves walking distance, but also disease-specific and general health-related Quality of Life (HRQoL). Therefore, we analyzed changes in HRQoL after endovascular leg revascularization in patients with chronic lower limb ischemia during a one-year follow-up. METHODS: The WHOQOL-BREF questionnaire was completed by 50 patients with intermittent claudication (IC) and 50 patients with chronic limb-threatening ischemia (CLTI) who underwent endovascular revascularization with a stent implantation, as well as 40 patients with IC not requiring endovascular intervention who received medical management only. The survey was completed before and then 3 and 12 months after an intervention. RESULTS: Patients with CLTI before endovascular intervention had the lowest HRQoL in the somatic, psychological, social, and environmental domains. After endovascular revascularization, these patients achieved the greatest improvement in HRQoL. Scores in the HRQoL domains correlated with Rutherford class, ankle-brachial index, and walking distance. The initial score in the somatic domain predicted the risk of target lesion revascularization (TLR) during the one-year follow-up. CONCLUSIONS: Endovascular leg revascularization improved patients' functioning, not only in the physical, but also in the psychological, environmental, and social domains of HRQoL. A higher score in the somatic domain of HRQoL before and at 3 months after an intervention predicted the risk of TLR during the one-year follow-up. It is recommended that scores for general HRQoL domains are added to the standard measures of the direct outcome of leg revascularization due to their one-year prognostic value.

Transcriptome and Proteome Analysis Revealed Key Pathways Regulating Final Stage of Oocyte Maturation of the Turkey (Meleagris gallopavo).

In birds, the zona pellucida (ZP) matrix that surrounds the ovulated oocyte-called the inner perivitelline layer-is involved in sperm-zona interaction and successful fertilization. To identify the important genes and proteins connected with the final step of egg development, next-generation sequencing and two-dimensional electrophoresis, combined with mass spectrometry, were used for the analysis of mature oocytes at the F1 developmental stage. A total of 8161 genes and 228 proteins were annotated. Six subfamilies of genes, with codes ZP, ZP1-4, ZPD, and ZPAX, were identified, with the dominant expression of ZPD. The main expression site for ZP1 was the liver; however, granulosa cells may also participate in local ZP1 secretion. A ubiquitination system was identified in mature oocytes, where ZP1 was found to be the main ubiquitinated protein. Analysis of transcripts classified in estrogen receptor (ESR) signaling indicated the presence of ESR1 and ESR2, as well as a set of estrogen-dependent genes involved in both genomic and nongenomic mechanisms for the regulation of gene expression by estrogen. Oxidative phosphorylation was found to be a possible source of adenosine triphosphate, and the nuclear factor erythroid 2-related factor 2 signaling pathway could be involved in the response against oxidative stress. Oocyte-granulosa cell communication by tight, adherens, and gap junctions seems to be essential for the final step of oocyte maturation.

Perspective on Stem Cell Therapy in Organ Fibrosis: Animal Models and Human Studies.

Tissue fibrosis is characterized by excessive deposition of extracellular matrix (ECM) components that result from the disruption of regulatory processes responsible for ECM synthesis, deposition, and remodeling. Fibrosis develops in response to a trigger or injury and can occur in nearly all organs of the body. Thus, fibrosis leads to severe pathological conditions that disrupt organ architecture and cause loss of function. It has been estimated that severe fibrotic disorders are responsible for up to one-third of deaths worldwide. Although intensive research on the development of new strategies for fibrosis treatment has been carried out, therapeutic approaches remain limited. Since stem cells, especially mesenchymal stem cells (MSCs), show remarkable self-renewal, differentiation, and immunomodulatory capacity, they have been intensively tested in preclinical studies and clinical trials as a potential tool to slow down the progression of fibrosis and improve the quality of life of patients with fibrotic disorders. In this review, we summarize in vitro studies, preclinical studies performed on animal models of human fibrotic diseases, and recent clinical trials on the efficacy of allogeneic and autologous stem cell applications in severe types of fibrosis that develop in lungs, liver, heart, kidney, uterus, and skin. Although the results of the studies seem to be encouraging, there are many aspects of cell-based therapy, including the cell source, dose, administration route and frequency, timing of delivery, and long-term safety, that remain open areas for future investigation. We also discuss the contemporary status, challenges, and future perspectives of stem cell transplantation for therapeutic options in fibrotic diseases as well as we present recent patents for stem cell-based therapies in organ fibrosis.

From Supramolecular Hydrogels to Multifunctional Carriers for Biologically Active Substances.

Supramolecular hydrogels are 3D, elastic, water-swelled materials that are held together by reversible, non-covalent interactions, such as hydrogen bonds, hydrophobic, ionic, host-guest interactions, and metal-ligand coordination. These interactions determine the hydrogels' unique properties: mechanical strength; stretchability; injectability; ability to self-heal; shear-thinning; and sensitivity to stimuli, e.g., pH, temperature, the presence of ions, and other chemical substances. For this reason, supramolecular hydrogels have attracted considerable attention as carriers for active substance delivery systems. In this paper, we focused on the various types of non-covalent interactions. The hydrogen bonds, hydrophobic, ionic, coordination, and host-guest interactions between hydrogel components have been described. We also provided an overview of the recent studies on supramolecular hydrogel applications, such as cancer therapy, anti-inflammatory gels, antimicrobial activity, controlled gene drug delivery, and tissue engineering.

Switching and Swapping of Quantum Information: Entropy and Entanglement Level.

Information switching and swapping seem to be fundamental elements of quantum communication protocols. Another crucial issue is the presence of entanglement and its level in inspected quantum systems. In this article, a formal definition of the operation of the swapping local quantum information and its existence proof, together with some elementary properties analysed through the prism of the concept of the entropy, are presented. As an example of the local information swapping usage, we demonstrate a certain realisation of the quantum switch. Entanglement levels, during the work of the switch, are calculated with the Negativity measure and a separability criterion based on the von Neumann entropy, spectral decomposition and Schmidt decomposition. Results of numerical experiments, during which the entanglement levels are estimated for systems under consideration with and without distortions, are presented. The noise is generated by the Dzyaloshinskii-Moriya interaction and the intrinsic decoherence is modelled by the Milburn equation. This work contains a switch realisation in a circuit form-built out of elementary quantum gates, and a scheme of the circuit which estimates levels of entanglement during the switch's operating.

Effect of Pig-Adipose-Derived Stem Cells' Conditioned Media on Skin Wound-Healing Characteristics In Vitro.

The primary mechanism by which adipose-derived stem cells (ASCs) exert their reparative or regenerative potential relies predominantly on paracrine action. Secretory abilities of ASCs have been found to be amplified by hypoxia pre-conditioning. This study investigates the impact of hypoxia (1% O2) on the secretome composition of pig ASCs (pASCs) and explores the effect of pASCs' conditioned media (CM) on skin cell functions in vitro and the expression of markers attributed to wound healing. Exposure of pASCs to hypoxia increased levels of vascular endothelial growth factor (VEGF) in CM-Hyp compared to CM collected from the cells cultured in normoxia (CM-Nor). CM-Hyp promoted the migratory ability of pig keratinocytes (pKERs) and delayed migration of pig dermal fibroblasts (pDFs). Exposure of pKERs to either CM-Nor or CM-Hyp decreased the levels of pro-fibrotic indicators WNT10A and WNT11. Furthermore, CM-Hyp enhanced the expression of KRT14, the marker of the basal epidermis layer. In contrast, CM-Nor showed a stronger effect on pDFs manifested by increases in TGFB1, COL1A1, COL3A1, and FN1 mRNA expression. The formation of three-dimensional endothelial cell networks was improved in the presence of CM-Hyp. Overall, our results demonstrate that the paracrine activity of pASCs affects skin cells, and this property might be used to modulate wound healing.

Histology Scoring System for Murine Cutaneous Wounds.

Monitoring wound progression over time is a critical aspect for studies focused on in-depth molecular analysis or on evaluating the efficacy of potential novel therapies. Histopathological analysis of wound biopsies can provide significant insight into healing dynamics, yet there is no standardized and reproducible scoring system currently available. The purpose of this study was to develop and statistically validate a scoring system based on parameters in each phase of healing that can be easily and accurately assessed using either Hematoxylin & Eosin (H&E) or Masson's Trichrome (MT) staining. These parameters included re-epithelization, epithelial thickness index, keratinization, granulation tissue thickness, remodeling, and the scar elevation index. The initial phase of the study was to (1) optimize and clarify healing parameters to limit investigator bias and variability; (2) compare the consistency of parameters assessed using H&E versus MT staining. During the validation phase of this study, the accuracy and reproducibility of this scoring system was independently iterated upon and validated in four different types of murine skin wound models (Excisional; punch biopsy; pressure ulcers; burn wounds). A total of n = 54 histology sections were randomized, blinded, and assigned to two groups of independent investigators (n = 5 per group) for analysis. The sensitivity of each parameter (ranging between 80% and 95%) is reported with illustrations on the appropriate assessment method using ImageJ software. In the validated scoring system, the lowest score (score:0) is associated with an open/unhealed wound as is evident immediately and within the first day postinjury, whereas the highest score (score:12) is associated with a completely closed and healed wound without excessive scarring. This study defines and describes the minimum recommended criteria for assessing wound healing dynamics using the SPOT skin wound score. The acronym SPOT refers to the academic and scientific institutions that were involved in the development of the scoring system, namely, Stellenbosch University, Polish Academy of Sciences, Obatala Sciences, and the University of Texas Southwestern.