Advanced approaches in skin wound healing - a review on the multifunctional properties of MXenes in therapy and sensing.

In recent years, the use of MXenes, a class of two-dimensional materials composed of transition metal carbides, nitrides, or carbonitrides, has shown significant promise in the field of skin wound healing. This review explores the multifunctional properties of MXenes, focusing on their electrical conductivity, photothermal effects, and biocompatibility in this field. MXenes have been utilized to develop advanced wound healing devices such as hydrogels, patches, and smart bandages for healing examination.

Integrated transcriptomics- and structure-based drug repositioning identifies drugs with proteasome inhibitor properties.

Computational pharmacogenomics can potentially identify new indications for already approved drugs and pinpoint compounds with similar mechanism-of-action. Here, we used an integrated drug repositioning approach based on transcriptomics data and structure-based virtual screening to identify compounds with gene signatures similar to three known proteasome inhibitors (PIs; bortezomib, MG-132, and MLN-2238). In vitro validation of candidate compounds was then performed to assess proteasomal proteolytic activity, accumulation of ubiquitinated proteins, cell viability, and drug-induced expression in A375 melanoma and MCF7 breast cancer cells.

L-Thyroxine and L-thyroxine-based antimicrobials against Streptococcus pneumoniae and other Gram-positive bacteria.

Objectives: The rise of antibiotic-resistant () poses a significant global health threat, urging the quest for novel antimicrobial solutions. We have discovered that the human hormone l-thyroxine has antibacterial properties. In order to explore its drugability we perform here the characterization of a series of l-thyroxine analogues and describe the structural determinants influencing their antibacterial efficacy.

The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses.

The COVID-19 pandemic has shown the need to develop effective therapeutics in preparedness for further epidemics of virus infections that pose a significant threat to human health. As a natural compound antiviral candidate, we focused on α-dystroglycan, a highly glycosylated basement membrane protein that links the extracellular matrix to the intracellular cytoskeleton. Here we show that the N-terminal fragment of α-dystroglycan (α-DGN), as produced in E.

A Modified Basophil Activation Test for the Clinical Management of Immediate Hypersensitivity Reactions to Paclitaxel: A Proof-of-Concept Study.

Immediate hypersensitivity reactions (iHSRs) to taxanes are observed in 6% and 4% of gynecologic and breast cancer patients, respectively. Drug desensitization is the only option, as no comparable alternative therapy is available. Surfactants in the taxane formulation have been implicated in the immunopathogenesis of iHSRs, although sporadic skin test (ST) positivity and iHSRs to nab-paclitaxel have suggested the involvement of the taxane moiety and/or IgE-mediated pathomechanisms.

Drug repurposing: a nexus of innovation, science, and potential.

The urgency of finding therapeutic solutions for emerging and existing health challenges has never been more pronounced. In the pursuit of this goal, the value of a strategy that makes use of existing resources is being recognized: drug repurposing or repositioning of compounds for new indications. Such approaches are employed against cancer, rheumatoid arthritis, multiple sclerosis, HIV/AIDS, and many other diseases.

Prediction of CD44 Structure by Deep Learning-Based Protein Modeling.

CD44 is a cell surface glycoprotein transmembrane receptor that is involved in cell-cell and cell-matrix interactions. It crucially associates with several molecules composing the extracellular matrix, the main one of which is hyaluronic acid. It is ubiquitously expressed in various types of cells and is involved in the regulation of important signaling pathways, thus playing a key role in several physiological and pathological processes.

Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells.

Diabetes-induced oxidative stress induces the development of vascular complications, which are significant causes of morbidity and mortality in diabetic patients. Among these, diabetic retinopathy (DR) is often caused by functional changes in the blood-retinal barrier (BRB) due to harmful oxidative stress events in lipids, proteins, and DNA. Docosahexaenoic acid (DHA) has a potential therapeutic effect against hyperglycemia-induced oxidative damage and apoptotic pathways in the main constituents of BRB, retinal pigment epithelium cells (ARPE-19).

Virtual screening and molecular dynamics simulations provide insight into repurposing drugs against SARS-CoV-2 variants Spike protein/ACE2 interface.

After over two years of living with Covid-19 and hundreds of million cases worldwide there is still an unmet need to find proper treatments for the novel coronavirus, due also to the rapid mutation of its genome. In this context, a drug repositioning study has been performed, using in silico tools targeting Delta Spike protein/ACE2 interface. To this aim, it has been virtually screened a library composed by 4388 approved drugs through a deep learning-based QSAR model to identify protein-protein interactions modulators for molecular docking against Spike receptor binding domain (RBD).

A chromosome-level genome assembly enables the identification of the follicule stimulating hormone receptor as the master sex-determining gene in the flatfish Solea senegalensis.

Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.

Liposome-based nanoparticles impact on regulatory and effector phenotypes of macrophages and T cells in multiple Sclerosis patients.

Current available treatments of Multiple Sclerosis (MS) reduce neuroinflammation acting on different targets on the immune system, but potentially lead to severe side effects and have a limited efficacy in slowing the progression of the disease. Here, we evaluated in vitro the immunomodulatory potential of a new class of nanoparticles - liposomes, constituted by a double-layer of phosphatidylserine (PSCho/PS), and double-faced, with an outer layer of phosphatidylserine and an inner layer of phosphatidic acid (PSCho/PA), either alone or in the presence of the myelin basic protein (MBP) peptide (residues 85-99) (PSCho/PS-MBP and PSCho/PA-MBP). Results showed that PSCho/PS are equally and efficiently internalized by pro- and anti-inflammatory macrophages (M1 and M2 respectively), while PSCho/PA were internalized better by M2 than M1.

The ,,-trimethylammonium moiety as tetrel bond donor site: crystallographic and computational studies.

Five structures bearing the ,,-trimethylammonium unit have been investigated to address the ability of the N-CH unit to function as a tetrel bond donor site. Charged and neutral electron density donors display close contacts with different carbon atoms of methyl groups on the ammonium moiety. The Hirshfeld atom refinement (HAR) technique was used on selected structures to accurately and precisely determine the hydrogen atom positions and, consequently, to get better insights into the N-C⋯Nu (Nu = nucleophile) interactions occurring in the crystals.

Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children.

Background. The profile of cellular immunological responses of children across the spectrum of COVID-19, ranging from acute SARS-CoV-2 infection to full recovery or Long COVID, has not yet been fully investigated. Methods.

Investigation of DHA-Induced Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells through the Combination of Metabolic Imaging and Molecular Biology.

Diabetes-induced oxidative stress leads to the onset of vascular complications, which are major causes of disability and death in diabetic patients. Among these, diabetic retinopathy (DR) often arises from functional alterations of the blood-retinal barrier (BRB) due to damaging oxidative stress reactions in lipids, proteins, and DNA. This study aimed to investigate the impact of the ω3-polyunsaturated docosahexaenoic acid (DHA) on the regulation of redox homeostasis in the human retinal pigment epithelial (RPE) cell line (ARPE-19) under hyperglycemic-like conditions.

Determination of Agrin and Related Proteins Levels as a Function of Age in Human Hearts.

Background: Mature cardiomyocytes are unable to proliferate, preventing the injured adult heart from repairing itself. Studies in rodents have suggested that the extracellular matrix protein agrin promotes cardiomyocyte proliferation in the developing heart and that agrin expression is downregulated shortly after birth, resulting in the cessation of proliferation. Agrin based therapies have proven successful at inducing repair in animal models of cardiac injury, however whether similar pathways exist in the human heart is unknown.

Cytoprotective Effect of Idebenone through Modulation of the Intrinsic Mitochondrial Pathway of Apoptosis in Human Retinal Pigment Epithelial Cells Exposed to Oxidative Stress Induced by Hydrogen Peroxide.

Idebenone is a ubiquinone short-chain synthetic analog with antioxidant properties, which is believed to restore mitochondrial ATP synthesis. As such, idebenone is investigated in numerous clinical trials for diseases of mitochondrial aetiology and it is authorized as a drug for the treatment of Leber's hereditary optic neuropathy. Mitochondria of retinal pigment epithelium (RPE) are particularly vulnerable to oxidative damage associated with cellular senescence.

A TLR/CD44 axis regulates T cell trafficking in experimental and human multiple sclerosis.

In the pathogenesis of autoimmune disorders, the modulation of leukocytes' trafficking plays a central role, still poorly understood. Here, we focused on the effect of TLR2 ligands in trafficking of T helper cells through reshuffling of isoforms repertoire. Concurrently, strain background and TLR2 haplotype affected Wnt/β-catenin signaling pathway and expression of splicing factors.

High degree of conservation of the enzymes synthesizing the laminin-binding glycoepitope of α-dystroglycan.

The dystroglycan (DG) complex plays a pivotal role for the stabilization of muscles in Metazoa. It is formed by two subunits, extracellular α-DG and transmembrane β-DG, originating from a unique precursor via a complex post-translational maturation process. The α-DG subunit is extensively glycosylated in sequential steps by several specific enzymes and employs such glycan scaffold to tightly bind basement membrane molecules.

Targeting SARS-CoV-2 Spike Protein/ACE2 Protein-Protein Interactions: a Computational Study.

The spike glycoprotein (S) of the SARS-CoV-2 virus surface plays a key role in receptor binding and virus entry. The S protein uses the angiotensin converting enzyme (ACE2) for entry into the host cell and binding to ACE2 occurs at the receptor binding domain (RBD) of the S protein. Therefore, the protein-protein interactions (PPIs) between the SARS-CoV-2 RBD and human ACE2, could be attractive therapeutic targets for drug discovery approaches designed to inhibit the entry of SARS-CoV-2 into the host cells.

Cytoprotective Effects of Punicalagin on Hydrogen-Peroxide-Mediated Oxidative Stress and Mitochondrial Dysfunction in Retinal Pigment Epithelium Cells.

The retinal pigment epithelium (RPE) is a densely pigmented, monostratified epithelium that provides metabolic and functional support to the outer segments of photoreceptors. Endogenous or exogenous oxidative stimuli determine a switch from physiological to pathological conditions, characterized by an increase of intracellular levels of reactive oxygen species (ROS). Accumulating evidence has elucidated that punicalagin (PUN), the major ellagitannin in pomegranate, is a potent antioxidant in several cell types.

organized neovascularization induced by 3D bioprinted endothelial-derived extracellular vesicles.

Extracellular vesicles (EVs) have become a key tool in the biotechnological landscape due to their well-documented ability to mediate intercellular communication. This feature has been explored and is under constant investigation by researchers, who have demonstrated the important role of EVs in several research fields ranging from oncology to immunology and diagnostics to regenerative medicine. Unfortunately, there are still some limitations to overcome before clinical application, including the inability to confine the EVs to strategically defined sites of interest to avoid side effects.

Unravelling the intricate photophysical behavior of 3-(pyridin-2-yl)triimidazotriazine AIE and RTP polymorphs.

The development of purely organic materials showing multicolor fluorescent and phosphorescent behaviour represents a formidable challenge in view of practical applications. Herein the rich photophysical behaviour of 3-(pyridin-2-yl)triimidazotriazine () organic molecule, comprising excitation-dependent fluorescence and phosphorescence under ambient conditions in both blended films and the crystalline phase, is investigated by means of steady state, time resolved and ultrafast spectroscopies and interpreted on the basis of X-ray diffraction studies and DFT/TDDFT calculations. In particular, by proper excitation wavelength, dual fluorescence and dual phosphorescence of molecular origin can be observed together with low energy phosphorescences resulting from aggregate species.

The hemoglobin Gly16β1Asp polymorphism in turbot (Scophthalmus maximus) is differentially distributed across European populations.

Turbot is an important flatfish widely distributed along the European coasts, whose fishery is centered in the North Sea. The commercial value of the species has boosted a successful aquaculture sector in Europe and China. Body growth is the main target of turbot breeding programs and is also a key trait related to local adaptation to temperature and salinity.